Effect of vitamin E supplementation in rheumatoid arthritis: a systematic review and meta-analysis

Haiyang Kou, Zhong Qing, Hao Guo, Rui Zhang, Jianbing Ma

Eur J Clin Nutr . 2022 Apr 25. doi: 10.1038/s41430-022-01148-9. Online ahead of print.


Objective: The purpose of this study was to evaluate the safety and effectiveness of vitamin E in rheumatoid arthritis patients.

Methods: A computerized search of PubMed, Embase, The Cochrane Library, and Web of Science databases was conducted to find published randomized controlled trials of vitamin E in rheumatoid arthritis; the experimental group was treated with vitamin E, while the control group was treated with placebo, other drugs, or external therapy; the search period was from the time each database was established to December 31, 2021, and a meta-analysis was conducted using Rev Man 5.4 software.

Results: This research eventually comprised nine publications with a total of 39,845 patients. Vitamin E supplementation was shown to be more effective in individuals with RA for sensitive joints (MD = -1.66, 95% CI – -6.32-2.99; I2 = 93%; P < 0.00001) and swollen joints (MD = -0.46, 95% CI – -1.98-1.07; I2 = 56%; P = 0.08).

Conclusions: Vitamin E’s ability to restore the intestinal barrier and improve the gastrointestinal tract may be linked to the prevention and treatment of rheumatoid arthritis. Vitamin E supplements used on a regular basis can help individuals with RA reduce joint discomfort, edema, and stiffness, as well as enhance their overall quality of life.

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Can Low-Dose of Dietary Vitamin E Supplementation Reduce Exercise-Induced Muscle Damage and Oxidative Stress? A Meta-Analysis of Randomized Controlled Trials

Myunghee Kim, Hyeyoon Eo, Josephine Gahyun Lim, Hyunjung Lim, Yunsook Lim

Nutrients . 2022 Apr 12;14(8):1599. doi: 10.3390/nu14081599.


Vitamin E plays an important role in attenuating muscle damage caused by oxidative stress and inflammation. Despites of beneficial effects from antioxidant supplementation, effects of antioxidants on exercise-induced muscle damage are still unclear. The aim of this meta-analysis was to investigate the effects of dietary vitamin E supplementation on exercise-induced muscle damage, oxidative stress, and inflammation in randomized controlled trials (RCTs). The literature search was conducted through PubMed, Medline, Science Direct, Scopus, SPORTDiscuss, EBSCO, Google Scholar database up to February 2022. A total of 44 RCTs were selected, quality was assessed according to the Cochrane collaboration risk of bias tool (CCRBT), and they were analyzed by Revman 5.3. Dietary vitamin E supplementation had a protective effect on muscle damage represented by creatine kinase (CK; SMD -1.00, 95% CI: -1.95, -0.06) and lactate dehydrogenase (SMD -1.80, 95% CI: -3.21, -0.39). Muscle damage was more reduced when CK was measured immediately after exercise (SMD -1.89, 95% CI: -3.39, -0.39) and subjects were athletes (SMD -5.15, 95% CI: -9.92, -0.39). Especially vitamin E supplementation lower than 500 IU had more beneficial effects on exercise-induced muscle damage as measured by CK (SMD -1.94, 95% CI: -2.99, -0.89). In conclusion, dietary vitamin E supplementation lower than 500 IU could prevent exercise-induced muscle damage and had greater impact on athletes.

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Effects of Vitamin E and Dietary Conditions on the Differentiation and Maturation of Osteoclast

Yoko Fujiwara, Yuko Ko, Mariko Sonoda, Ikuyo Ichi, Tomoko Ishikawa

J Nutr Sci Vitaminol (Tokyo) . 2022;68(1):73-77. doi: 10.3177/jnsv.68.73.


α-Tocopherol is reported to activate the differentiation and fusion of osteoclast, however, it is not clear whether the excessive intake of vitamin E is a risk for osteoporosis. To investigate the effects of vitamin E and the dietary conditions on the osteoclastogenesis, osteoclast differentiation was evaluated using the bone marrow cells collected from mice fed various dietary conditions. Not only α-tocopherol but also γ-tocotrienol activated osteoclast differentiation in mice fed normal diet. Formation of large multinucleated cells was significantly increased by stimulation of nuclear factor-kappa B ligand (RANKL) in mice fed vitamin E deficient diet and was suppressed by the addition of α-tocopherol. Furthermore, there was no effect on bone density and no difference in osteoclast differentiation from the bone marrow cells collected from mice fed a high-fat diet with 0 or 1,000 mg/kg diet of α-tocopherol and tocotrienol, respectively. These results suggest that different type of diet affect the activation of osteoclast by α-tocopherol.

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The Protective Effects of γ-Tocotrienol on Muscle Stem Cells Through Inhibiting Reactive Oxidative Stress Production

Shuo Yang, Juan Yang, Huiwen Zhao, Rong Deng, Hancheng Fan, Jinfu Zhang, Zihao Yang, Huihong Zeng, Bohai Kuang, Lijian Shao

Front Cell Dev Biol . 2022 Mar 15;10:820520. doi: 10.3389/fcell.2022.820520. eCollection 2022.


Pseudotrophic muscular dystrophy is a common clinical skeletal muscle necrotic disease, among which Duchenne muscular dystrophy (DMD) is the predominant. For such diseases, there is no clinically effective treatment, which is only symptomatic or palliative treatment. Oxidative stress and chronic inflammation are common pathological features of DMD. In recent years, it has been found that the pathophysiological changes of skeletal muscle in DMD mice are related to muscle stem cell failure. In the present study, we established a DMD mice model and provided tocotrienol (γ-tocotrienol, GT3), an antioxidant compound, to explore the relationship between the physiological state of muscle stem cells and oxidative stress. The results showed that the application of GT3 can reduce ROS production and cellular proliferation in the muscle stem cells of DMD mice, which is beneficial to promote the recovery of muscle stem cell function in DMD mice. GT3 treatment improved the differentiation ability of muscle stem cells in DMD mice with increasing numbers of MyoD+ cells. GT3 application significantly decreased percentages of CD45+ cells and PDGFRα+ fibro-adipogenic progenitors in the tibialis anterior of DMD mice, indicating that the increased inflammation and fibro-adipogenic progenitors were attenuated in GT3-treated DMD mice. These data suggest that increased ROS production causes dysfunctional muscle stem cell in DMD mice, which might provide a new avenue to treat DMD patients in the clinic.

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Vitamin E in the treatment of tardive dyskinesia: a meta-analysis

Hongyan Xu, Haoqiang Qin, Shaohua Chen, Mingjian Guan

Int Clin Psychopharmacol . 2022 Mar 1;37(2):60-66. doi: 10.1097/YIC.0000000000000387.


Long-term use of antipsychotic drugs is associated with tardive dyskinesia. At present, there is no satisfactory treatment for tardive dyskinesia. Some randomized trials suggested that vitamin E can improve tardive dyskinesia. This study was undertaken to evaluate the effects of vitamin E treatment for tardive dyskinesia. We searched internet databases for randomized controlled trials. A total of 21 studies including 854 patients with tardive dyskinesia were included in this meta-analysis. Eighteen studies reported the Abnormal Involuntary Movements Scale (AIMS) as the primary outcome. After vitamin E treatment, a decrease of 2.36 (95% CI = -3.27 to -1.45; P < 0.00001) in the AIMS was observed in the treatment group, compared with the control group. Vitamin E may offer a new avenue treatment for tardive dyskinesia.

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Alpha-tocopherol-loaded polycaprolactone nanoparticles improve the inflammation and systemic oxidative stress of arthritic rats

Lucas S Moreira, Any Carolina Chagas, Ana Paula Ames-Sibin, Vanesa O Pateis, Odinei H Gonçalves, Francielli Maria S Silva-Comar, Luzmarina Hernandes, Anacharis B Sá-Nakanishi, Lívia Bracht, Ciomar A Bersani-Amado, Adelar Bracht, Jurandir F Comar

J Tradit Complement Med . 2021 Dec 24;12(4):414-425. doi: 10.1016/j.jtcme.2021.12.003. eCollection 2022 Jul.


Background and aim: The present study investigated the effects of orally administered α-tocopherol-loaded polycaprolactone nanoparticles on the articular inflammation and systemic oxidative status of middle-aged Holtzman rats with Freund’s adjuvant-induced polyarthritis, a model for rheumatoid arthritis. Intraperitoneally administered free α-tocopherol provided the reference for comparison.

Experimental procedure: Two protocols of treatment were followed: intraperitoneal administration of free α-tocopherol (100 mg/kg i.p.) or oral administration of free and nanoencapsulated α-tocopherol (100 mg/kg p.o.). Animals were treated during 18 days after arthritis induction.

Results: Free (i.p.) and encapsulated α-tocopherol decreased the hind paws edema, the leukocytes infiltration into femorotibial joints and the mRNA expression of pro-inflammatory cytokines in the tibial anterior muscle of arthritic rats, but the encapsulated compound was more effective. Free (i.p.) and encapsulated α-tocopherol decreased the high levels of reactive oxygen species in the brain and liver, but only the encapsulated compound decreased the levels of protein carbonyl groups in these organs. Both free (i.p.) and encapsulated α-tocopherol increased the α-tocopherol levels and the ratio of reduced to oxidized glutathione in these organs.

Conclusion: Both intraperitoneally administered free α-tocopherol and orally administered encapsulated α-tocopherol effectively improved inflammation and systemic oxidative stress in middle-aged arthritic rats. However, the encapsulated form should be preferred because the oral administration route does not be linked to the evident discomfort that is caused in general by injectable medicaments. Consequently, α-tocopherol-loaded polycaprolactone nanoparticles may be a promising adjuvant to the most current approaches aiming at rheumatoid arthritis therapy.

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Tocotrienol Supplementation Led to Higher Serum Levels of Lysophospholipids but Lower Acylcarnitines in Postmenopausal Women: A Randomized Double-Blinded Placebo-Controlled Clinical Trial

Chwan-Li Shen, Huanbiao Mo, Dale M Dunn, Bruce A Watkins

Front Nutr . 2021 Dec 24;8:766711. doi: 10.3389/fnut.2021.766711. eCollection 2021.


Osteoporosis is a major health problem in postmenopausal women. Herein we evaluated the effects of 12-week tocotrienols (TT) supplementation on serum metabolites in postmenopausal, osteopenic women. Eighty-nine participants (59.7 ± 6.8 yr, BMI 28.7 ± 5.7 kg/m2) were assigned to 3 treatments: placebo (860 mg olive oil/day), 300mg TT (300 mg TT/day), and 600mg TT (600 mg TT/day) for 12 weeks. TT consisted of 90% δ-TT and 10% γ-TT. In this metabolomic study, we evaluated the placebo and 600mgTT at baseline and 12 weeks. As expected, TT and its metabolite levels were higher in the supplemented group after 12 weeks. At baseline, there were no differences in demographic parameters or comprehensive metabolic panels (CMP). Metabolomics analysis of serum samples revealed that 48 biochemicals were higher and 65 were lower in the 600mg TT group at 12 weeks, compared to baseline. The results confirmed higher serum levels of tocotrienols and lysophospholipids, but lower acylcarnitines and catabolites of tryptophan and steroids in subjects given 600mg TT. In summary, 12-week TT supplementation altered many serum metabolite levels in postmenopausal women. The present study supports our previous findings that TT supplementation helps reduce bone loss in postmenopausal osteopenic women by suppressing inflammation and oxidative stress. Furthermore, the body incorporates TT which restructures biomembranes and modifies phospholipid metabolism, a response potentially linked to reduced inflammation and oxidative stress.

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γ-Tocotrienol induced the proliferation and differentiation of MC3T3-E1 cells through the stimulation of the Wnt/β-catenin signaling pathway

Weili Xu, Yutong Li, Rennan Feng, Pan He, Yuqi Zhang

Food Funct . 2021 Dec 15. doi: 10.1039/d1fo02583j. Online ahead of print.


γ-Tocotrienol (γ-T3), an isoprenoid phytochemical, has shown the promotion of osteoblast proliferation and differentiation in our previous study. In this study, its underlying mechanism was investigated through regulating the Wnt/β-catenin signaling pathway in MC3T3-E1 cells. Comparative experiment results showed that γ-T3, not α-tocopherol (α-TOC) increased more significantly the viability and differentiation in MC3T3-E1 cells. After that, the cells were incubated with 10 mM LiCl, or 4 μM γ-T3 with or without 1 μM XAV-939. γ-T3 at 4 μM stimulated the Wnt/β-catenin signaling pathway by increasing the expression and nuclear accumulation of β-catenin, and the expressions of their downstream factors, such as cyclin-D1, c-Myc, BMP2 and BMP-4 in MC3T3-E1 cells. γ-T3 not only upregulated the viability, induced G0/G1 to the S phase, and promoted the expressions of PCNA (Proliferating Cell Nuclear Antigen) and Ki-67, but also increased ALP activity and the expressions of ON, OPN and OCN. Moreover, the effects of γ-T3 on the MC3T3-E1 cells resembled the actions of LiCl, an activator of the Wnt/β-catenin signaling pathway. Notably, all these effects of γ-T3 on the MC3T3-E1 cells were completely blocked by the Wnt/β-catenin signaling pathway inhibitor XAV-939. Our data demonstrated that γ-T3 can target β-catenin to enhance the Wnt/β-catenin signaling pathway, which led to increased expressions of the downstream cell proliferation and cell cycle-associated (cyclin D1 and c-myc), and cell differentiation-associated (BMP-2 and BMP-4) target genes, and ultimately promoted MC3T3-E1 cell proliferation and differentiation. Therefore, γ-T3 may be a potential agent to prevent and reverse osteoporosis due to its safety and powerful abilities of osteogenesis.

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Vitamin E-Enhanced Liners in Primary Total Hip Arthroplasty: A Systematic Review and Meta-Analysis

Qian-Yue Cheng, Bin-Fei Zhang, Peng-Fei Wen, Jun Wang, Lin-Jie Hao, Tao Wang, Hui-Guang Cheng, Ya-Kang Wang, Jian-Bin Guo, Yu-Min Zhang

Biomed Res Int . 2021 Dec 6;2021:3236679. doi: 10.1155/2021/3236679. eCollection 2021.


Objective: Adding vitamin E to highly cross-linked polyethylene liners is frequently performed in clinical practice, aiming at reducing liner wear, increasing liner survival, and delaying revision surgery. This study is aimed at evaluating the revision rate, total femoral head penetration, and postoperative clinical function of highly cross-linked polyethylene liners with and without vitamin E in total hip arthroplasty.

Methods: We conducted a systematic literature search to identify the use of highly cross-linked vitamin E liners compared to other liners in patients who received total hip arthroplasty (THA) before April 2021. The study quality assessment and data collection were conducted by two independent reviewers. Studies were artificially grouped, and vitamin E-enhanced liners (VE-PE) were compared with vitamin E-free liners (non-VE-PE). Analyses were executed using Review Manager version 5.4.1.

Results: From the preliminary screening of 568 studies, fourteen studies met the research criteria. Compared to non-VE-PE, using VE-PE reduced the all-cause revision rate (odds ratio = 0.54; 95% confidence interval (CI) 0.40, 0.73; P < 0.0001). The total femoral head penetration of the VE-PE was lower than that of the non-VE-PE (mean difference = -0.10; 95% CI -0.17, -0.03; P = 0.007). However, there was no difference in clinical function, including the Harris Hip Score and EuroQol Five-Dimension Questionnaire scores.

Conclusion: Compared to the liners without vitamin E, the addition of vitamin E to liners could reduce the all-cause revision rate by approximately 46% in the short-term follow-up. In addition, even though addition of vitamin E could also slow down femoral head penetration, there is no contribution to clinical function.

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The role of Vitamin E in hip implant-related corrosion and toxicity: Initial outcome

Vikas Manjunath, Ravindra V Badhe, Maureen McCoy, Josiah Rynne, Aisha Bhatti, Abhijith Segu, Ebru Oral, Joshua J Jacobs, Paul Chastain, Divya Bijukumar, Mathew T Mathew

J Mech Behav Biomed Mater . 2021 Nov;123:104769. doi: 10.1016/j.jmbbm.2021.104769. Epub 2021 Aug 11.


In orthopedic healthcare, Total Hip Replacement (THR) is a common and effective solution to hip-related bone and joint diseases/fracture; however, corrosion of the hip implant and the release of degradation metal ions/particles can lead to early implant failure and pose potential toxicity risk for the surrounding tissues. The main objective of this work was to investigate the potential role of Vitamin E to minimize corrosion-related concerns from CoCrMo hip implants. The study focused on two questions (i) Can Vitamin E inhibit CoCrMo corrosion? and (ii) Does Vitamin E moderate the toxicity associated with the CoCrMo implant particles? In the study (i) the electrochemical experiments (ASTM G61) with different concentrations of Vitamin E (1, 2, 3 mg/ml against the control) were performed using normal saline and simulated synovial fluid (Bovine calf serum-BCS, 30 g/L protein, pH 7.4) as electrolytes. The polished CoCrMo disc (Ra 50 nm) was the working electrode. The findings suggested that both Vitamin E-Saline (45 ± 0.9%) and Vitamin E-BCS (91 ± 3%) solutions protected against implant corrosion at a Vitamin E concentration of 3 mg/ml, but Vitamin E-BCS showed protection at all Vitamin E (1-3 mg/ml) concentration levels. These results suggested that the Vitamin E and the protein present in the BCS imparted additive effects towards the electrochemical inhibition. In the study (ii) the role of Vitamin E in cytotoxicity inhibition was studied using a mouse neuroblastoma cell line (N2a) for CoCrMo particles and Cr ions separately. The CoCrMo particles were generated from a custom-built hip simulator. The alamarBlue assay results suggested that Vitamin E provides significant protection (85% and 75% proliferation) to N2a cells against CoCrMo particles and Cr ions, respectively at 1 μg/ml concentration, as compared to the control group. However, the results obtained from ROS expression and DNA fiber staining suggest that Vitamin E is only effective against CoCrMo degradation particles and not against Cr ions. In summary, the findings show that Vitamin E can minimize the corrosion processes and play a role in minimizing the potential toxicity associated with implants.

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