Alterations of Serum Vitamin E and Vitamin A Concentrations of Ponies and Horses During Experimentally Induced Obesity

Carola Schedlbauer, Dominique Blaue, Jens Raila, Ingrid Vervuert

J Anim Physiol Anim Nutr (Berl) . 2020 May 14. doi: 10.1111/jpn.13385. Online ahead of print.


Vitamin A, vitamin E and retinol-binding protein 4 (RBP4) are a focus of current obesity research in humans. The impact of body weight (BW) gain on fat-soluble vitamins and its associated parameters in equines has not been previously reported. Ten Shetland ponies and 9 Warmblood horses, all adult geldings, non-obese and healthy, were fed an excessive energy diet for 20 months to induce BW gain. Serum α-tocopherol (vitamin E), retinol (vitamin A), retinol-binding protein 4 (RBP4) and retinol/RBP4 ratio were analysed before BW gain induction and at six timepoints during the BW gaining period. The mean (±SD) % BW gain achieved during two years of excess energy intake was 29.9 ± 19.4% for ponies and 17 ± 6.74% for horses. Serum α-tocopherol increased significantly in ponies and horses during excess energy intake and circulating α-tocopherol levels correlated positively with α-tocopherol intake (r = .6; p < .001). Serum retinol concentrations showed variations during the study but without relation to intake. Serum RBP4 decreased at the end of the study. The retinol/RBP4 ratio increased with BW gain without differences between ponies and horses. In comparison with human research, the increase in the retinol/RBP4 ratio was unexpected and needs further elucidation.

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Comparative Study of the Oxidation Stability of High Oleic Oils and Palm Oil During Thermal Treatment

Ziyang Xu, Zhan Ye, Youdong Li, Jinwei Li, Yuanfa Liu

J Oleo Sci . 2020 May 14. doi: 10.5650/jos.ess19307. Online ahead of print.


For the controversy still existed about the oxidation stability of the high oleic oils compared with palm oil (PO), this study was aimed to explore the possible reason causing the controversies. Total polar compounds (TPC) was used to evaluate the oxidation stability of oils. Results showed there exist two kinds of lineal changes about the content of total polar compounds (TPC) in each oil, which were closely linked with the fatty acid composition and the tocochromanols content. The possible influence of the initial quality of oils also should be considered. The TPC of high oleic peanut oil (HOPO), high oleic sunflower oil (HOSO), high oleic rapeseed oil (HORO) and PO increased slowly at the initial period mainly owing to the antioxidation of tocochromanols, then sharply after 24, 48, 36 and 72 h respectively, when tocochromanols in each oil almost reduced below the detection limit. After that, the major factor would be fatty acids, particularly PUFA. It showed that the major tocochromanols in different oils (e.g. α, γ-tocotrienols in PO, α, γ-tocopherols in HORO and HOPO, and α-tocopherols in HOSO), could impose the main effects of inhibiting the TPC generation in the initial thermal treatment. The TPC in HORO significantly increased after 84 hours of heat process, which might be caused by the higher content of the polyunsaturated fatty acids (PUFA) (i.e. C18:2 and C18:3). However, the content of the saturated fatty acid (SFA) did not show statistically significant change during the thermal treatment.

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Vitamin E Promotes the Inverse Hexagonal Phase via a Novel Mechanism: Implications for Antioxidant Role

Paul E Harper, Andres T Cavazos, Jacob J Kinnun, Horia I Petrache, Stephen R Wassall

Langmuir . 2020 May 12;36(18):4908-4916. doi: 10.1021/acs.langmuir.0c00176. Epub 2020 Apr 30.


Vitamin E (α-tocopherol) and a range of other biological compounds have long been known to promote the HII (inverted hexagonal) phase in lipids. Now, it has been well established that purely hydrophobic lipids such as dodecane promote the HII phase by relieving extensive packing stress. They do so by residing deep within the hydrocarbon core. However, we argue from X-ray diffraction data obtained with 1-palmitoyl-2-oleoylphosphatidylcholine (POPE) and 1,2-dioleoylphosphatidylcholine (DOPE) that α-tocopherol promotes the HII phase by a different mechanism. The OH group on the chromanol moiety of α-tocopherol anchors it near the aqueous interface. This restriction combined with the relatively short length of α-tocopherol (as compared to DOPE and POPE) means that α-tocopherol promotes the HII phase by relieving compressive packing stress. This observation offers new insight into the nature of packing stress and lipid biophysics. With the deeper understanding of packing stress offered by our results, we also explore the role that molecular structure plays in the primary function of vitamin E, which is to prevent the oxidation of polyunsaturated membrane lipids.

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Protective Effect of Vitamin E on Sperm Parameters in Rats Infected With Candida Albicans

Arash Babaei, Nasrin Kheradmand, Maryam Baazm, Negin Nejati, Mohamad Khalatbari

Andrologia . 2020 May 12;e13593. doi: 10.1111/and.13593


Candida albicans is one of the most frequent pathogens present in the reproductive system. The negative in vitro effects of C. albicans on sperm functions have previously been studied. The current study was undertaken to investigate the effects of C. albicans infection in vivo on sperm quality and to evaluate the efficacy of vitamin E administration in rats infected with C. albicans. In this study, 5 days after infection induction, animals were treated with vitamin E for 5 weeks. Thereafter, sperm parameters, lipid peroxidation (LPO), total antioxidant capacity (TAC), hormonal analysis and testis histology were evaluated. Based on the results, sperm parameters and TAC significantly reduced, while LPO and tissue damage increased (p ≤ .05) following the infection. Hormone analysis showed low LH and testosterone levels in serum of the infected rats. Treatment with vitamin E significantly (p ≤ .05) improved sperm quality and testis histology, increased TAC and reduced LPO. In addition, vitamin E administration significantly increased (p ≤ .05) serum LH and testosterone levels. These results clearly indicate that vitamin E is effective in attenuating the adverse effects of C. albicans infection on male fertility and could be used as a complementary treatment for patients who suffer from fertility disorders following C. albicans infection.

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Metabolism and Biological Activity of α-Tocopherol Derived From Vitamin E-enriched Transgenic Maize in Broilers

Zhan Tengfei, Han Yunsheng, Tang Chaohua, Zhao Qingyu, Sun Dandan, Li Ying, Jia Xueting, Zhou Lingyun, Zhang Junmin

J Sci Food Agric . 2020 May 9. doi: 10.1002/jsfa.10480


Background: The aim of this study was to investigate the metabolism of α-tocopherol derived from vitamin E-enriched transgenic maize (VER) and its effects on antioxidant and immune functions in broilers aged 1 to 42 days. A total of 360 1-day-old male broilers were randomly divided into three groups containing six replicates with 20 broilers per replicate. The negative control (NC) group and the positive control (PC) group were given non-GM maize and non-GM maize plus exogenous vitamin E (VE), respectively, and the VER group was given VER replacing the non-GM maize given to the NC group. Between days 1 and 21 and days 22 and 42, VE levels were 4.38 and 4.63 mg kg-1 in the NC group, and 14.11 and 14.91 mg kg-1 in the PC and VER group, respectively.

Results: The results showed that α-tocopherol from both VER and additives increased α-tocopherol transfer protein and cytochrome P450 concentrations. Additionally, serum α-tocopherol and α-tocopherylquinone levels of broilers in the PC and VER groups were significantly higher than those in the NC group (P < 0.05). Compared with the NC group, broilers in both groups that received α-tocopherol had reduced NF-κB p65 concentrations, significantly decreased serum prostaglandin E2 , IL-6, malondialdehyde, and hydrogen peroxide levels (P < 0.05), and significantly increased glutathione, glutathione peroxidase, and total antioxidant capacity (P < 0.05).

Conclusion: In summary, both VER and non-GM maize fortified with exogenous VE showed similar effects on broilers, indicating that the α-tocopherol in VER has sufficient biological activity.

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High-throughput Profiling Reveals Perturbation of Endoplasmic Reticulum Stress-Related Genes in Atherosclerosis Induced by High-Cholesterol Diet and the Protective Role of Vitamin E

Perinur Bozaykut, Ruchan Ekren, Osman Ugur Sezerman, Vadim N Gladyshev, Nesrin Kartal Ozer

Biofactors . 2020 May 8. doi: 10.1002/biof.1635.


Formation of atherosclerotic plaques, called atherogenesis, is a complex process affected by genetic and environmental factors. It was proposed that endoplasmic reticulum (ER) stress is an important factor in the pathogenesis of atherosclerosis and that vitamin E affects atherosclerotic plaque formation via its antioxidant properties. Here, we investigated ER stress-related molecular mechanisms in high-cholesterol diet (HCD, 2%)-induced atherosclerosis model and the role of vitamin E supplementation in it, beyond its antioxidant properties. The consequences of HCD and vitamin E supplementation were examined by determining protein levels of ER stress markers in aortic tissues. As vitamin E supplementation acts on several unfolded protein response (UPR) factors, it decreased ER stress induced by HCD. To elucidate the associated pathways, gene expression profiling was performed, revealing differentially expressed genes enriched in ER stress-related pathways such as the proteasome and the apoptosis pathways. We further assessed the proteasomal activity impaired by HCD in the aorta and showed that vitamin E reversed it to that of control animals. Overall, the study characterized the effects of HCD and vitamin E on ER stress-related gene expression, revealing the role of proteolytic systems during atherogenesis.

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A Meta-Analysis and Meta-Regression of the Effects of Vitamin E Supplementation on Serum Enrichment, Udder Health, Milk Yield, and Reproductive Performance of Transition Cows

MohammadHossein Moghimi-Kandelousi, Ali A Alamouti, Mahdi Imani, Qendrim Zebeli

J Dairy Sci . 2020 May 7;S0022-0302(20)30346-5. doi: 10.3168/jds.2019-17556.


Vitamin E is an essential nutrient for cows, but the effect of vitamin E supplementation is often controversially discussed in the published literature. The main goal of this meta-analysis was to evaluate the effects of vitamin E supplementation on its serum and colostrum enrichment, milk yield (MY), and somatic cell counts (SCC), as well as on various reproductive variables of transition cows, by considering a large set of variables that might influence the responses to vitamin E supplementation. After a broad search in journals and databases with keywords related to transition cows supplemented with vitamin E and appropriate filtering of the results, 36 papers including 53 trials were selected, and their data were extracted into a database. A meta-analysis was conducted on the extracted data. The analysis showed enrichment of serum vitamin E both at parturition (effect size: 2.423) and postpartum (effect size: 0.473), but no effects of vitamin E supplementation on IgG concentration in colostrum (effect size: -0.05) were found. There was a tendency for supplemented cows to produce more milk (effect size: 1.29) during the first month of lactation. Because of large heterogeneity, a meta-regression was performed but none of the presumed influencing factors was identified as a potential variable affecting MY. Milk SCC, as an indicator of udder health, was unaffected by vitamin E supplementation. Vitamin E supplementation tended to decrease the calving to first estrus period (CFP), whereby supplementing Se and taking parity into account in the analysis significantly lowered the CFP. Cows receiving additional vitamin E had, on average, 6.1% fewer cases of retained placenta, whereby Se supplementation and breed were key factors improving the effect of vitamin E to reduce retained placenta. In this regard, breeds other than Holstein responded better and these cows showed a lower incidence of retained placenta. The supplemented cows showed fewer days open (effect size: -0.31), and this improvement was affected linearly by increasing the dosage administered. Also, cows showed fewer services per conception with increasing dosage of vitamin E. In conclusion, this analysis showed that supplementing vitamin E did not affect SCC or colostrum quality but improved reproductive performance of transition cows, an effect consistent with increased levels of serum vitamin E and, for some variables, being modulated by Se supplementation.

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The Neurotoxic Effect of Long-Term Use of High-Dose Pregabalin and the Role of Alpha Tocopherol in Amelioration: Implication of MAPK Signaling With Oxidative Stress and Apoptosis

Sarah Hamed N Taha, Hala Saied Zaghloul, Abla Abd El Rahman Ali, Iman Fawzy Gaballah, Laila Ahmed Rashed, Basma Emad Aboulhoda

Naunyn Schmiedebergs Arch Pharmacol . 2020 May 6. doi: 10.1007/s00210-020-01875-5.


Pregabalin abuse has become an emerging concern; thus, the current study has been designed to study the neurotoxic hazards of prolonged high-dose of pregabalin (akin to that abused by addicts) and to evaluate the effect of alpha tocopherol as a possible ameliorating agent. The current study evaluated the brain neurotransmitters; dopamine, glutamate, and norepinephrine. The study also assessed the expression of the apoptosis-related markers Bax, Bcl2, and caspase 3. Western-blotted analysis of the three major mitogen-activated protein kinases (MAPKs), the c-JUN N-terminal kinase (JNK), the p38 MAPK, and the extracellular signal-regulated kinase (ERK), has also been performed. The study also evaluated oxidative stress via assessment of the cortical tissue levels of reduced glutathione and malondialdehyde and the activity of superoxide dismutase. Histopathological examination and histomorphometric evaluation of the darkly degenerated cortical neurons have also been performed. Pregabalin in high doses (150 mg/kg/day and 300 mg/kg/day) disrupted the ERK/JNK/p38-MAPK signaling, reversed the bax/bcl2 ratio, and induced oxidative stress. It also diminished the release of dopamine, glutamate, and norepinephrine and increased the count of degenerated neurons. Alpha tocopherol treatment significantly attenuated the deleterious effects induced by pregabalin. The role of alpha tocopherol in ameliorating the oxidative stress injury, and apoptosis induced by pregabalin, along with its role in normalizing neurotransmitters, modulating the ERK/JNK/p38-MAPK signaling pathways and improving the histopathological cortical changes, offers alpha tocopherol as a promising adjunctive therapy in patients undergoing prolonged pregabalin therapy as those suffering from prolonged seizures and neuropathies.

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Efficacy of Vitamin E in Methotrexate-Induced Hepatotoxicity in Rheumatoid Arthritis: An Open-Label Case-Control Study

Binit Vaidya, Manisha Bhochhibhoya, Shweta Nakarmi

Int J Rheumatol . 2020 May 1;2020:5723485. doi: 10.1155/2020/5723485.


Objective: To examine the efficacy of vitamin E in methotrexate- (MTX-) induced transaminitis in patients with rheumatoid arthritis (RA).

Methods: A case-control study was conducted at a tertiary rheumatology center for 12 months. Patients with RA on MTX and deranged aminotransferases were included. Patients with previous liver diseases, baseline transaminitis before methotrexate initiation, alcohol intake, muscle diseases, under hepatotoxic drugs, and aminotransferases > 3 times the upper normal limit were excluded. The patients were divided into treatment (vitamin E 400 mg bid for 3 months) and control groups (no vitamin E) using a random number table. The dose of MTX was unaltered. Follow-up was done after 3 and 6 months. Independent t-test was done to compare means of two groups. Paired t-test was done to compare differences in mean.

Results: Among 230 patients, 86.5% were female with a mean BMI of 25.9 ± 4.5 kg/m2. In the treatment group, SGPT and SGOT at baseline were 73.1 ± 20.4 and 60.2 ± 24.5 IU/L, respectively; at 3-month follow-up 44.6 ± 34.2 and 38.3 ± 20.8 IU/L, respectively; and at 6-month follow-up 40.4 ± 35.7 and 34.2 ± 21.9 IU/L, respectively. In the control group, SGPT and SGOT at baseline were 63.4 ± 15.1 and 46.8 ± 13.7 IU/L, respectively, and at 3-month follow-up 55.8 ± 45.9 and 45.5 ± 30.9 IU/L, respectively. Significant decrease in the level of aminotransferases was seen in the treatment group (p value < 0.001) and not in the control group (p values 0.161 and 0.728, respectively). The change in levels of SGPT and SGOT from baseline to 3 months of follow-up was statistically significant in between two study groups (p values 0.007 and <0.001, respectively). From the control group, 29 patients were crossed over to vitamin E for the next 3 months. SGPT and SGOT decreased from 97.6 ± 44.1 to 46.1 ± 40.9 and 69.3 ± 34.9 to 29.1 ± 11.6 IU/L, respectively (p values 0.031 and 0.017, respectively).

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Randomized, Placebo-Controlled Clinical Trial Combining Pentoxifylline-Tocopherol and Clodronate in the Treatment of Radiation-Induced Plexopathy

Delanian SE, Lenglet T, Maisonobe T, Resche-Rigon M, Pradat PF

Int J Radiat Oncol Biol Phys. 2020 May 1;107(1):154-162. doi: 10.1016/j.ijrobp.2020.01.002. Epub 2020 Jan 24.



Radiation-induced (RI) plexopathy is a rare peripheral nerve injury after radiation therapy for cancer. No treatment has been shown to slow its progression. A pentoxifylline-vitamin E combination significantly reduced RI fibrosis, and its association with clodronate (PENTOCLO) allowed healing of osteoradionecrosis and reduction of neurologic symptoms in phase 2 trials.


A placebo-controlled, double-blind trial conducted in adults with RI limb plexopathy without cancer recurrence, randomized in 2 arms to PENTOCLO (pentoxifylline 800 mg, tocopherol 1000 mg, clodronate 1600 mg 5 days per week) or triple placebo. The primary outcome measure after 18 months of treatment was the neurologic Subjective Objective Management Analytic (SOMA) score evaluating pain, paresthesia, and motor disability.


Between 2011 and 2015, 59 patients were included: 1 false inclusion (neoplastic plexopathy), 29 treated with placebo (group P), and 29 treated with the active drugs (group A); 46 patients presented an upper-limb and 12 a lower-limb plexopathy. The mean delay after irradiation was 26 ± 8 years, for patients with neurologic symptoms for 5 ± 5 years. The median global SOMA scores in the P and A groups, respectively, were 9 (range, 6-11) versus 9 (range, 8-11) at M0 and 9 (range, 5-12) versus 10 (range, 6-11) at M18 without any significant difference. Analysis of the secondary outcomes showed that SOMA score subdomains for pain and paresthesia were more affected in group A (not significant). The frequency of adverse events was similar in the 2 groups (81% of patients): slight expected vascular-gastrointestinal symptoms in A, but a large excess of RI complications (arterial stenosis).


This first randomized drug trial in RI plexopathy failed to show a beneficial effect. More studies are needed in patients with less advanced disease and fewer confounding comorbidities and with a more sensitive measure to detect a therapeutic effect.

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