Vitamin E as promising adjunct treatment option in the combat of infectious diseases caused by bacterial including multi-drug resistant pathogens – Results from a comprehensive literature survey

Minnja S Hartmann, Soraya Mousavi, Stefan Bereswill, Markus M Heimesaat

Eur J Microbiol Immunol (Bp) . 2020 Nov 5. doi: 10.1556/1886.2020.00020. Online ahead of print.

Abstract

The use of antibiotics has provoked an emergence of various multidrug-resistant (MDR) bacteria. Infectious diseases that cannot be treated sufficiently with conventional antibiotic intervention strategies anymore constitue serious threats to human health. Therefore, current research focus has shifted to alternative, antibiotic-independent therapeutic approaches. In this context, vitamin E constitutes a promising candidate molecule due to its multi-faceted modes of action. Therefore, we used the PubMed database to perform a comprehensive literature survey reviewing studies addressing the antimicrobial properties of vitamin E against bacterial pathogens including MDR bacteria. The included studies published between 2010 and 2020 revealed that given its potent synergistic antimicrobial effects in combination with distinct antibiotic compounds, vitamin E constitutes a promising adjunct antibiotic treatment option directed against infectious diseases caused by MDR bacteria such as Pseudomonas aeruginosa, Burkholderia cenocepacia and methicillin-resistant Staphylococcus aureus (MRSA). In conclusion, the therapeutic value of vitamin E for the treatment of bacterial infections should therefore be investigated in future clinical studies.

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Negative Correlation Between Vitamin A and Positive Correlation Between Vitamin E and Inflammation Among Healthy Adults in Korea: Based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2016-2018 7th Edition

Ki-Hong Hong, Young Lee

J Inflamm Res . 2020 Oct 29;13:799-811. doi: 10.2147/JIR.S265856. eCollection 2020.

Abstract

Purpose: Vitamins exert its effect through different isoforms. The isoform conversion phases involved are affected outside factors. Here, we investigated the correlation between serum retinol, α-tocopherol, and serum inflammatory markers using stratified data acquired from 2016 to 2018 Korea National Health and Nutrition Examination Survey (KNHANES).

Materials and methods: This study was based on data acquired from the 7th edition (2016-2018) of the Korea National Health and Nutrition Examination Survey, consisting of survey data on smoking and alcohol drinking, serum retinol level, serum α-tocopherol level, high-sensitivity C-reactive protein (hs-CRP), and baseline characteristics.

Results: There was a negative correlation between serum retinol and hs-CRP in alcohol drinking men. There was a negative correlation between serum retinol and hs-CRP in the alcohol-nonsmoking female group. There was a positive correlation between α-tocopherol and hs-CRP in the nonsmoking and alcohol-drinking group. There was a positive correlation between α-tocopherol and hs-CRP in the nonsmoking and alcohol-drinking female group. There was positive correlation between vitamin A and E and metabolic syndrome. The lowest vitamin A level was observed in subjects with all five metabolic syndrome criteria matched.

Conclusion: There was a negative correlation between serum retinol and hs-CRP and positive correlation between α-tocopherol and hs-CRP. Absorption and secretion of serum retinol are affected by inflammation status through retinol-binding protein. Alcohol acts as a competitive inhibitor of vitamin A oxidation through alcohol dehydrogenase and ALDH activity. Smoking causes inflammation and induces reactive oxygen species scavenging system and increases cytochrome p450 levels. These factors may have contributed to the observed findings. Metabolic syndrome subjects increased as the levels of vitamin A and vitamin E increased. Since obesity is inversely related to ALDH activity, we postulate that patients with metabolic syndrome may also have low ALDH activity, especially in the Asian population. Future studies are warranted to study the efficacy of ALDH or ALDH inducers in patients with vitamin A deficiency or metabolic syndrome.

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Vitamin C and vitamin C plus E improve the immune function in the elderly

Mónica De la Fuente, Carmen Sánchez, Carmen Vellejo, Estefanía Díaz-Del Cerro, Francisco Arnalich, Ángel Hernanz

Exp Gerontol . 2020 Oct 19;111118. doi: 10.1016/j.exger.2020.111118. Online ahead of print.

Abstract

With aging the immune response is impaired. This immunosenescence, in which an alteration of the redox state of the immune cells appears, is involved in the rate of aging. Since leukocyte function is a good marker of health and predictor of longevity, the effects of daily oral administration of the antioxidant vitamin C (500 mg), or both vitamin C (500 mg) and vitamin E (200 mg) on several blood neutrophil (adherence, chemotaxis, phagocytosis, and superoxide anion levels) and lymphocyte (adherence, chemotaxis, proliferation, interleukin-2 secretion and natural killer activity) functions were studied in healthy elderly men and women. These parameters were analysed before supplementation, after 3 months of supplementation, and 6 months after the end of supplementation. The results showed that vitamin C, in elderly participants, improved the immune functions studied which achieved values close to those of young adults. These effects were maintained in several functions after 6 months without supplementation. Similar effects were found in the elderly supplemented with both vitamin C and E. Thus, a short period of vitamin C or vitamin C and E ingestion, with the doses used, improves the immune function in elderly men and women and could contribute to a healthy longevity.

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Supplementation with Resveratrol, Piperine and Alpha-Tocopherol Decreases Chronic Inflammation in a Cluster of Older Adults with Metabolic Syndrome

Raúl Francisco Pastor, Marisa Gabriela Repetto, Fabiana Lairion, Alberto Lazarowski, Amalia Merelli, Zulma Manfredi Carabetti, Isabel Pastor, Elena Pastor, Laura Valeria Iermoli, Carlos Amadeo Bavasso, Roberto Héctor Iermoli

Nutrients . 2020 Oct 15;12(10):E3149. doi: 10.3390/nu12103149.

Abstract

Metabolic Syndrome (MetS) is increasing worldwide regardless of culture, genetic, gender, and geographic differences. While multiple individual risk factors, such as obesity, hypertension, diabetes, and hyperlipidemia, can cause cardiovascular disease (CVD), it is the intercurrence of these risk factors that defines MetS as a cluster that creates an environment for atherosclerosis and other manifestations of CVD. Despite the advances in the knowledge and management of each of the components of MetS, there are two molecular biology processes, chronic inflammation and oxidative stress, which are still underdiagnosed and undertreated. In order to assess the effect of a dietary supplement on chronic inflammation in MetS, we conducted a clinical trial with volunteers receiving a formula composed of resveratrol, piperine and alpha tocopherol (FRAMINTROL®), together with their habitual treatment, for three months. The inflammatory state was evaluated by ultrasensitive C reactive protein (US CRP) and ferritin in plasma, and oxygen consumption and chemiluminescence in neutrophils. The results showed that ferritin decreased by 10% (p < 0.05), US-CRP by 33% (p < 0.0001), oxygen consumption by 55% (p < 0.0001), and spontaneous chemiluminiscence was by 25% (p < 0.005) after treatment. As far as we know, this is the first study showing a chronic inflammation decrease in MetS patients due to the administration of a biopower Resveratrol-piperine and alpha tocopherol dietary supplement together with conventional therapy.

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The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials

Omid Asbaghi, Mehdi Sadeghian, Behzad Nazarian, Mehrnoosh Sarreshtedari, Hassan Mozaffari-Khosravi, Vahid Maleki, Mohammad Alizadeh, Azad Shokri, Omid Sadeghi

Sci Rep . 2020 Oct 14;10(1):17234. doi: 10.1038/s41598-020-73741-6.

Abstract

The previous meta-analysis of clinical trials revealed a beneficial effect of vitamin E supplementation on serum C-reactive protein (CRP) concentrations; however, it is unknown whether this vitamin has the same influence on other inflammatory biomarkers. Also, several clinical trials have been published since the release of earlier meta-analysis. Therefore, we aimed to conduct a comprehensive meta-analysis to summarize current evidence on the effects of vitamin E supplementation on inflammatory biomarkers in adults. We searched the online databases using relevant keywords up to November 2019. Randomized clinical trials (RCTs) investigating the effect of vitamin E, compared with the placebo, on serum concentrations of inflammatory cytokines were included. Overall, we included 33 trials with a total sample size of 2102 individuals, aged from 20 to 70 years. Based on 36 effect sizes from 26 RCTs on serum concentrations of CRP, we found a significant reduction following supplementation with vitamin E (- 0.52, 95% CI – 0.80, – 0.23 mg/L, P < 0.001). Although the overall effect of vitamin E supplementation on serum concentrations of interleukin-6 (IL-6) was not significant, a significant reduction in this cytokine was seen in studies that used α-tocopherol and those trials that included patients with disorders related to insulin resistance. Moreover, we found a significant reducing effect of vitamin E supplementation on tumor necrosis factor-α (TNF-α) concentrations at high dosages of vitamin E; such that based on dose-response analysis, serum TNF-α concentrations were reduced significantly at the dosages of ≥ 700 mg/day vitamin E (Pnon-linearity = 0.001). Considering different chemical forms of vitamin E, α-tocopherol, unlike other forms, had a reducing effect on serum levels of CRP and IL-6. In conclusion, our findings revealed a beneficial effect of vitamin E supplementation, particularly in the form of α-tocopherol, on subclinical inflammation in adults. Future high-quality RCTs should be conducted to translate this anti-inflammatory effect of vitamin E to the clinical setting.

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Antioxidant activity of Hydroxytyrosol and Vitamin E reduces systemic inflammation in children with paediatric NAFLD

Antonella Mosca, Annalisa Crudele, Antonella Smeriglio, Maria Rita Braghini, Nadia Panera, Donatella Comparcola, Arianna Alterio, Maria Rita Sartorelli, Giulia Tozzi, Massimiliano Raponi, Domenico Trombetta, Anna Alisi

Dig Liver Dis . 2020 Oct 12;S1590-8658(20)30920-8. doi: 10.1016/j.dld.2020.09.021. Online ahead of print.

Abstract

Background: The rise in paediatric non-alcoholic fatty liver disease (NAFLD) is particularly alarming. We recently reported that Hydroxytyrosol (HXT) and Vitamin E (VitE) may improve oxidative stress, insulin resistance, and steatosis in children with biopsy-proven NAFLD.

Aim: Here, we investigated if HXT+VitE may reduce systemic inflammation in the above-mentioned patients.

Methods: This study analysed the plasma levels of IL (interleukin)-6, IL-1β, IL-10, tumour necrosis factor (TNF)-α, 4‑hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2’deoxyguanosine (8-OHdG) in children enrolled in the HXT+VitE trial (ClinicalTrials.gov, NCT02842567).

Results: Changes in markers of systemic inflammation were found in both placebo (Pla) and HXT+VitE. In particular, after four months, the levels of IL-1β and TNF-α were reduced in both groups, while IL-6 decreased, and IL-10 increased significantly only in the group treated with HXT+VitE. Children treated with HXT+VitE showed a significant decrease of 4-HNE and 8-OHdG that correlated with the improvement of triglyceride levels. Noticeably, only the 8-OHdG decrease correlated with steatosis amelioration and with the increase of IL-10 levels.

Conclusion: The treatment with HXT and VitE reduced the NAFLD-related systemic inflammation in children, mainly by an increase of IL-10 circulating levels that occurred in response to DNA damage recovery, ultimately improving steatosis and hypertriglyceridemia.

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The effect of vitamin E and selenium combination in repairing fluoride-induced DNA damage to NRK-52E cells

Veysel Yüksek, Sedat Çetin, Ayşe Usta

Mol Biol Rep . 2020 Oct;47(10):7761-7770. doi: 10.1007/s11033-020-05852-2. Epub 2020 Oct 6.

Abstract

Prolonged and excessive fluoride exposure can lead to fluorosis. The kidney is one of the organs that are injured mostly due to fluoride-induced damage. Fluoride can induce DNA damage at cytotoxic concentrations. This study aims to determine the extent of NaF-induced DNA damage and to investigate the effect of vitamin E and selenium combination (ES) in preventing and repairing this damage. For this purpose, we administered different combinations of NaF and ES to NRK-52E cells and determined the effective concentrations of ES and the NaF IC50 values associated with different incubation times (3, 12, and 24 h) by using the MTT assay. The determined quantities of NaF IC50 in association with time and the NaF IC50 + ES combination were administered to the cells. The extent of DNA damage was determined with the comet assay and the expression levels of the Ku70/80 and PARP-1 genes were determined with the RT-qPCR method. DNA damage significantly increased in all experimental groups compared to the control group (p < 0.05). It was found out that the NaF and ES combination statistically reduced the DNA damage compared to the damage observed in the NaF-treated groups (p < 0.05). Treatment of the ES combination significantly increased the expressions of Ku70 and Ku80 genes involved in DNA repair (p < 0.05). We concluded that vitamin E and selenium can potentially be effective in the repair of fluoride-induced DNA damage based on the results of this in vitro study. Our results may shed light on the prevention of DNA damage associated with fluorosis.

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The effects of royal jelly and tocotrienol-rich fraction on impaired glycemic control and inflammation through irisin in obese rats

Pardis Irandoost, Naimeh Mesri Alamdari, Atoosa Saidpour, Farzad Shidfar, Neda Roshanravan, Mohammad Asghari Jafarabadi, Farnaz Farsi, Nazanin Asghari Hanjani, Mohammadreza Vafa

J Food Biochem . 2020 Oct 5;e13493. doi: 10.1111/jfbc.13493. Online ahead of print.

Abstract

The effects of royal jelly (RJ) and tocotrienol-rich fraction (TRF) on obesity-induced glucose intolerance and inflammation were assessed in the current study. Regarding irisin as an important adipomyokine that attenuates obesity-induced disorders, we evaluated whether RJ and TRF could exert their metabolism regulatory effects through irisin. Obese rats were fed a high-fat diet (HFD) with or without supplementation of RJ, TRF, or both, for 8 weeks. At the end of the intervention, weight, irisin, glycemic, and inflammatory indices were measured. The weight of the rats did not remarkably reduce in any of the groups. Glucose homeostasis and inflammation were improved when we added RJ and TRF to HFD. RJ elevated irisin concentration, but the effect of TRF on irisin was not noticeable. Our results indicated that, despite the lack of significant weight loss, RJ and TRF promoted healthy obesity. This improvement was mediated by irisin in RJ consuming rats. PRACTICAL APPLICATIONS: Obesity is a public health concern associated with several chronic disorders. The beneficial effects of irisin on obesity-related disorders are well-established. It is the first study assessing the effect of RJ and TRF as functional foods, with pharmacological and nutritional activities on obesity complications, through irisin mediation. Our study demonstrated that RJ exerts its metabolic regulatory effects by irisin as a mediator. Our investigation makes a remarkable contribution to the literature, because it suggests a new mechanism for the anti-obesity properties of RJ and TRF.

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Vitamin C and E Treatment Blunts Sprint Interval Training-Induced Changes in Inflammatory Mediator-, Calcium-, and Mitochondria-Related Signaling in Recreationally Active Elderly Humans

Victoria L Wyckelsma, Tomas Venckunas, Marius Brazaitis, Stefano Gastaldello, Audrius Snieckus, Nerijus Eimantas, Neringa Baranauskiene, Andrejus Subocius, Albertas Skurvydas, Mati Pääsuke, Helena Gapeyeva, Priit Kaasik, Reedik Pääsuke, Jaak Jürimäe, Brigitte A Graf, Bengt Kayser, Nicolas Place, Daniel C Andersson, Sigitas Kamandulis, Håkan Westerblad

Antioxidants (Basel) . 2020 Sep 17;9(9):E879. doi: 10.3390/antiox9090879.

Abstract

Sprint interval training (SIT) has emerged as a time-efficient training regimen for young individuals. Here, we studied whether SIT is effective also in elderly individuals and whether the training response was affected by treatment with the antioxidants vitamin C and E. Recreationally active elderly (mean age 65) men received either vitamin C (1 g/day) and vitamin E (235 mg/day) or placebo. Training consisted of nine SIT sessions (three sessions/week for three weeks of 4-6 repetitions of 30-s all-out cycling sprints) interposed by 4 min rest. Vastus lateralis muscle biopsies were taken before, 1 h after, and 24 h after the first and last SIT sessions. At the end of the three weeks of training, SIT-induced changes in relative mRNA expression of reactive oxygen/nitrogen species (ROS)- and mitochondria-related proteins, inflammatory mediators, and the sarcoplasmic reticulum Ca2+ channel, the ryanodine receptor 1 (RyR1), were blunted in the vitamin treated group. Western blots frequently showed a major (>50%) decrease in the full-length expression of RyR1 24 h after SIT sessions; in the trained state, vitamin treatment seemed to provide protection against this severe RyR1 modification. Power at exhaustion during an incremental cycling test was increased by ~5% at the end of the training period, whereas maximal oxygen uptake remained unchanged; vitamin treatment did not affect these measures. In conclusion, treatment with the antioxidants vitamin C and E blunts SIT-induced cellular signaling in skeletal muscle of elderly individuals, while the present training regimen was too short or too intense for the changes in signaling to be translated into a clear-cut change in physical performance.

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Dietary Intervention Accelerates NASH Resolution Depending on Inflammatory Status with Minor Additive Effects on Hepatic Injury by Vitamin E Supplementation

Julie Hviid Klaebel, Günaj Rakipovski, Birgitte Andersen, Jens Lykkesfeldt, Pernille Tveden-Nyborg

Antioxidants (Basel) . 2020 Sep 1;9(9):E808. doi: 10.3390/antiox9090808.

Abstract

Despite the lack of effective pharmacotherapy against nonalcoholic steatohepatitis (NASH) and liver fibrosis, vitamin E (vitE) supplementation and lifestyle modifications are recommended for the management of NASH due to promising clinical results. We recently reported a positive effect of supplementation with 800 IU vitE and atorvastatin on NASH resolution in guinea pigs. In the present study, we investigated the effect of high-dose vitE therapy combined with dietary intervention against progressive NASH and advanced fibrosis in the guinea pig model. Sixty-six guinea pigs received either high-fat (HF) or standard guinea pig chow diet (Control) for 25 weeks. Prior to eight weeks of intervention, HF animals were allocated into groups; dietary intervention (Chow) or dietary intervention with 2000 IU/d vitE supplementation (CvitE). Both Chow and CvitE reduced dyslipidemia, hepatic lipid accumulation and liver weight (p < 0.05), while CvitE further decreased hepatocellular ballooning (p < 0.05). Subanalyses of individual responses within intervention groups showed significant correlation between the hepatic hallmarks of NASH and lipid accumulation vs. inflammatory state (p < 0.05). Collectively, our results indicate that individual differences in sensitivity towards intervention and inflammatory status determine the potential beneficial effect of dietary intervention and high-dose vitE supplementation. Moreover, the study suggests that inflammation is a primary target in NASH treatment.

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