Monthly Archives: May 2021

Dynamics of Serum Retinol and Alpha-Tocopherol Levels According to Non-Alcoholic Fatty Liver Disease Status

Dongsub Jeon, Minkook Son, Juhyun Shim

Nutrients . 2021 May 19;13(5):1720. doi: 10.3390/nu13051720.

Abstract

The available data on the association between micronutrients in the blood and non-alcoholic fatty liver disease (NAFLD) are limited. To investigate the clinical implications of this relationship, we sought to identify the difference in the serum levels of vitamins A and E according to NAFLD status using data from the seventh Korea National Health and Nutrition Examination Survey. In this cross-sectional study of the Korean population, NAFLD and its severity were defined using prediction models. Differences in the prevalence and severity of NAFLD were analyzed according to serum retinol (vitamin A) and alpha (α)-tocopherol (vitamin E) levels. Serum levels of retinol and α-tocopherol were positively correlated with the prevalence of NAFLD. In most prediction models of the NAFLD subjects, serum retinol deficiency was significantly correlated with advanced fibrosis, while serum α-tocopherol levels did not differ between individuals with or without advanced fibrosis. Similar trends were also noted with cholesterol-adjusted levels of α-tocopherol. In summary, while circulating concentrations of retinol and α-tocopherol were positively associated with the presence of NAFLD, advanced liver fibrosis was only correlated with serum retinol levels. Our findings could provide insight into NAFLD patient care at a micronutrient level.

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Risk of Colorectal Cancer in a Brazilian Population is Differentially Associated with the Intake of Processed Meat and Vitamin E

Radmila Raiani Alves Ribeiro, Isabella Rolim de Brito, Karolline Andrade Souza, Larissa de Castro Souza, Tiago Almeida de Oliveira, Mathias Weller

Nutr Cancer . 2021 May 17;1-10. doi: 10.1080/01635581.2021.1926519. Online ahead of print.

Abstract

The incidence and mortality rates of colorectal cancer (CRC) in Northeast Brazil are increasing. To study the association between CRC and diet, data were obtained from 64 patients with CRC and 123 sex- and age-matched controls. The dietary details were recorded using a validated food frequency questionnaire. Nutrient intake was calculated using Dietsys software (National Cancer Institute, Maryland, USA). In a binary logistic regression model of dietary components (model 1), the chance of CRC increased by 0.2% (odds ratio [OR] = 1.002; 95% confidence interval [CI]: 1.000-1.004) for each gram of processed meat intake per week (p < 0.010). Consumption of eggs decreased the chance by 0.1% per gram (OR = 0.999; 95% CI: 0.998-1.000; p < 0.050). The use of oil (including olive oil) for served food decreased the chance by 1.8% (OR = 0.982; 95% CI: 0.970-0.992) for each time consumed (p < 0.010). In a model of nutritional factors (model 2), intake of vitamin E decreased the chance by 16.8% (OR = 0.832; 95% CI: 0.725-0.940) for each milligram intake per week (p < 0.010). In model 1 and 2 smoking increased the chance of CRC by 10.294 (95%CI: 4.240-27.670) and 2.496 (95% CI: 1.425-3.566) times (p < 0.010; p < 0.010), respectively.

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Simultaneous quantification of vitamin E and vitamin E metabolites in equine plasma and serum using LC-MS/MS

Hadi Habib, Carrie J Finno, Ingrid Gennity, Gianna Favro, Erin Hales, Birgit Puschner, Benjamin C Moeller

J Vet Diagn Invest . 2021 May;33(3):506-515. doi: 10.1177/10406387211005433. Epub 2021 Apr 13.

Abstract

Vitamin E deficiencies can impact normal growth and development in humans and animals, and assessment of circulating levels of vitamin E and its metabolites may be an important endpoint for evaluation. Development of a sensitive method to detect and quantify low concentrations of vitamin E and metabolites in biological specimens allows for a proper diagnosis for patients and animals that are deficient. We developed a method to simultaneously extract, detect, and quantify the vitamin E compounds alpha-tocopherol (α-TP), gamma-tocopherol (γ-TP), alpha-tocotrienol (α-TT), and gamma-tocotrienol (γ-TT), and the corresponding metabolites formed after β-oxidation of α-TP and γ-TP, alpha-carboxymethylbutyl hydroxychroman (α-CMBHC) and alpha- or gamma-carboxyethyl hydroxychroman (α- or γ-CEHC), respectively, from equine plasma and serum. Quantification was achieved through liquid chromatography-tandem mass spectrometry. We applied a 96-well high-throughput format using a Phenomenex Phree plate to analyze plasma and serum. Compounds were separated by using a Waters ACQUITY UPLC BEH C18 column with a reverse-phase gradient. The limits of detection for the metabolites and vitamin E compounds were 8-330 pg/mL. To validate the method, intra-day and inter-day accuracy and precision were evaluated along with limits of detection and quantification. The method was then applied to determine concentrations of these analytes in plasma and serum of horses. Alpha-TP levels were 3-6 µg/mL of matrix; the metabolites were found at much lower levels, 0.2-1.0 ng/mL of matrix.

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Vitamin E for the Prevention of Chemotherapy-Induced Peripheral Neuropathy: A meta-Analysis

Jie Chen, Haili Shan, Wenjun Yang, Jiali Zhang, Haibin Dai, Ziqi Ye

Front Pharmacol . 2021 May 13;12:684550. doi: 10.3389/fphar.2021.684550. eCollection 2021.

Abstract

Background: Vitamin E has been increasingly used to prevent chemotherapy-induced peripheral neuropathy (CIPN) in recent years. However, it is still unclear whether vitamin E can effectively prevent CIPN. Methods: We searched all clinical studies in the Embase, Cochrane Library, Clinicaltrials.gov, and PubMed databases from inception to December 2020. We performed a meta-analysis of 9 randomized controlled trials (RCTs) with 486 patients that compared the vitamin E group with the control group. Outcomes of the study were incidence of all-grade CIPN, incidence of severe CIPN, and the total neuropathy scores (TNS). Random effect models were used to make the meta-analysis results more cautious. Results: Notably, vitamin E significantly reduced the incidence of all-grade CIPN (overall risk ratio (RR) = 0.55, 95% CI: 0.36, 0.85, I2 = 77.3%, p = 0.007), and TNS (overall standard mean difference (SMD) = -0.64, 95% CI: –1.03, -0.25, I2 = 42.7%, p = 0.001). However, the results of the subgroup analysis, which included only double-blind RCTs, suggested that vitamin E did not significantly reduce the incidence of all-grade CIPN (overall RR = 0.52, 95% CI: 0.07, 4.06, I2 = 77.5%, p = 0.531). Moreover, there was no significant difference in the incidence of severe CIPN between these two arms (p = 0.440). Conclusion: The results of our meta-analysis suggests that vitamin E has a beneficial effect on the incidence and symptoms of CIPN. However, routine prophylactic use of vitamin E is still not recommended. Moreover, more high-quality double-blind RCTs are needed to further validate the effects of vitamin E in prevention of CIPN.

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Vitamin E regulates bovine granulosa cell apoptosis via NRF2-mediated defence mechanism by activating PI3K/AKT and ERK1/2 signalling pathways

Meimei Wang, Yan Li, Yanxia Gao, Qiufeng Li, Yufeng Cao, Yizhao Shen, Panliang Chen, Jinling Yan, Jianguo Li

Reprod Domest Anim . 2021 May 12. doi: 10.1111/rda.13950. Online ahead of print.

Abstract

High-yield dairy cows are usually subject to high-intensive cell metabolism and produce excessive reactive oxygen species (ROS). Once ROS is beyond the threshold of scavenging ability, it can induce oxidative stress, imperilling the reproductive performance of cows. The study was to investigate the effects of vitamin E (VE) on H2 O2 -induced proliferation and apoptosis of bovine granulosa cells and the underlying molecular mechanism. Granulosa cells were pretreated with VE for 24 hr and then treated with H2 O2 for 6 hr. The results showed that VE treatment decreased the intracellular ROS levels, increased the MDA content, and improved the antioxidant enzyme activity in a dose-dependent manner. Furthermore, VE treatment promoted the proliferation and inhibited apoptosis in granulosa cells by up-regulation of CCND1 and BCL2 levels and down-regulation of P21, BAX, and CASP3 levels. The cytoprotective effects of VE were attributed to the activation of the NRF2 signalling pathway. Knockdown of the NRF2 impaired the cytoprotective effects of VE on granulosa cells. Besides, the PI3K/AKT and ERK1/2, but not the p38 signalling pathway is involved in the regulation of VE-mediated cell proliferation and apoptosis. The PI3K/AKT inhibitor LY294002 and ERK1/2 inhibitor SCH772984 inhibited the VE-induced granulosa cell proliferation and promoted apoptosis, whereas the p38 inhibitor SB203580 had the opposite effects. These results were confirmed by proliferation and apoptosis-related gene expression at mRNA and protein levels. The results also showed that the PI3K/AKT inhibitor LY294002 and ERK1/2 inhibitor SCH772984 inhibited VE-induced NRF2, GCLC, GCLM, and HO-1 expression, whereas the p38 inhibitor SB203580 not. Overall, the results demonstrated that VE-regulated granulosa cell proliferation and apoptosis via NRF2-mediated defence system by activating the PI3K/AKT and ERK1/2 signalling pathway.

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Endogenous vitamin E metabolites mediate allosteric PPARγ activation with unprecedented co-regulatory interactions

Sabine Willems, Leonie Gellrich, Apirat Chaikuad, Stefan Kluge, Oliver Werz, Jan Heering, Stefan Knapp, Stefan Lorkowski, Manfred Schubert-Zsilavecz, Daniel Merk

Cell Chem Biol . 2021 May 12;S2451-9456(21)00212-9. doi: 10.1016/j.chembiol.2021.04.019. Online ahead of print.

Abstract

Vitamin E exhibits pharmacological effects beyond established antioxidant activity suggesting involvement of unidentified mechanisms. Here, we characterize endogenously formed tocopherol carboxylates and the vitamin E mimetic garcinoic acid (GA) as activators of the peroxisome proliferator-activated receptor gamma (PPARγ). Co-stimulation of PPARγ with GA and the orthosteric agonist pioglitazone resulted in additive transcriptional activity. In line with this, the PPARγ-GA complex adopted a fully active conformation and interestingly contained two bound GA molecules with one at an allosteric site. A co-regulator interaction scan demonstrated an unanticipated co-factor recruitment profile for GA-bound PPARγ compared with canonical PPARγ agonists and gene expression analysis revealed different effects of GA and pioglitazone on PPAR signaling in hepatocytes. These observations reveal allosteric mechanisms of PPARγ modulation as an alternative avenue to PPARγ targeting and suggest contributions of PPARγ activation by α-13-tocopherolcarboxylate to the pharmacological effects of vitamin E.

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Low Serum Vitamin E Level Associated with Low Hand Grip Strength in Community-Dwelling Adults: Korean National Health and Nutrition Examination Survey (KNHANES VII) 2016-2018

Yongjae Kim, Sungjae Shin, Namki Hong, Yumie Rhee

Nutrients . 2021 May 11;13(5):1598. doi: 10.3390/nu13051598.

Abstract

This study assessed the association between serum vitamin E levels and hand grip strength (HGS) in community-dwelling adults data of 1011 men aged 50 years and older and 1144 postmenopausal women were analyzed. Low HGS was defined as HGS below the sex-stratified median value. Proportion of low HGS was the greatest in the lowest quintile of serum vitamin E level (<10.51 mg/L, 57.1%), with a decreasing trend toward the highest vitamin E quintile (>17.81 mg/L, 43.6%; p < 0.001). A one-unit (mg/L) decrease in vitamin E levels was associated with lower HGS in men (adjusted beta coefficient -0.10, 95% confidence interval [CI] -0.18 to -0.02, p = 0.019), but not in women (-0.01, 95% CI -0.06 to 0.03, p = 0.550). Compared with the middle quintile (Q3; 12.59-14.69 mg/L), the lowest vitamin E quintile (Q1) was associated with elevated odds of low HGS (adjusted odds ratio [aOR]: 1.38, p = 0.045), independent of sociodemographic factors, health-related lifestyles, comorbidities, dietary intake, and cholesterol level. However, the odds of low HGS did not differ significantly in other vitamin E quintiles (Q2, aOR 1.12; Q4, aOR 1.38; Q5, aOR 1.12; p > 0.05). Individuals with the lowest quintile vitamin E level had elevated odds of low HGS independent of covariates, findings which merit further validation.

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Tocotrienols Ameliorate Neurodegeneration and Motor Deficits in the 6-OHDA-Induced Rat Model of Parkinsonism: Behavioural and Immunohistochemistry Analysis

Mangala Kumari, Premdass Ramdas, Ammu Kutty Radhakrishnan, Methil Kannan Kutty, Nagaraja Haleagrahara

Nutrients . 2021 May 10;13(5):1583. doi: 10.3390/nu13051583.

Abstract

Parkinson’s disease (PD) is a debilitating neurodegenerative disease, which progresses over time, causing pathological depigmentation of the substantia nigra (SN) in the midbrain due to loss of dopaminergic neurons. Emerging studies revealed the promising effects of some nutrient compounds in reducing the risk of PD. One such nutrient compound that possess neuroprotective effects and prevents neurodegeneration is tocotrienol (T3), a vitamin E family member. In the present study, a single dose intracisternal injection of 250 µg 6-hydroxydopamine (6-OHDA) was used to induce parkinsonism in male Sprague Dawley (SD) rats. Forty-eight hours post injection, the SD rats were orally supplemented with alpha (α)- and gamma (γ)-T3 for 28 days. The neuroprotective effects of α- and γ-T3 were evaluated using behavioural studies and immunohistochemistry (IHC). The findings from this study revealed that supplementation of α- and γ-T3 was able to ameliorate the motor deficits induced by 6-OHDA and improve the neuronal functions by reducing inflammation, reversing the neuronal degradation, and preventing further reduction of dopaminergic neurons in the SN and striatum (STR) fibre density.

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Vitamin E and selenium improve mesenchymal stem cell conditioned media immunomodulatory effects

Fereshteh Ghasemi, Majid Khoshmirsafa, Elahe Safari, Marzieh Asgari, Mehdi Alemrajabi, Shahrzad Nojehdehi, Samane Khorrami

Stem Cell Investig . 2021 May 7;8:9. doi: 10.21037/sci-2020-008. eCollection 2021.

Abstract

Background: Mesenchymal stem cells (MSCs) with immunoregulatory properties affect immune systems. Many studies showed that antioxidants such as vitamin E (Vit E) and selenium (Se) could improve stem cells survival. This study aims to investigate the effects of MSC conditioned media (CM) treated with Vit E and Se on immune cells.

Methods: MSCs were isolated and cultured with Vit E and Se. Immature dendritic cells (DCs) and peripheral blood mononuclear cells (PBMCs) were cultured with MSC CM treated with Vit E and Se. The expression of HLA-DR, CD86, CD40, and CD83 on mature DC were evaluated. DC supernatant and PBMCs supernatant was collected for the study of TGF-β, IL-10, and IL-12. PBMCs evaluated for the expression of T-bet, GATA3, RORγt, and FOXP3.

Results: MSC CM increased CD40 on myeloid DC (mDC). CD40 has been decreased in DC treated with MSC (Vit E) and MSC (Se) CM. HLA-DR expression on DCs and IL-12 level were significantly reduced in MSC (Vit E) CM. IL-10 concentration increased in DCs treated with MSC (Vit E) and MSC (Se) CM. Treatment of PBMCs with MSC CM decreased IL-10 level, FOXP3, and RORγt expression. On the other hand, the MSC (Vit E) CM and MSC (Se) CM decreased the IL-10 level and increased IL-12, T-bet, and RORγt.

Conclusions: According to the results, the treatment of MSC with Vit E and Se enhanced the ability of MSCs to inhibit DCs and improved immunomodulatory effects. Concerning the effect of MSC on PBMC, it seems that it increased RORγt expression through monocytes.

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