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



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


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.


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).


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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Fig. 1: Flow chart of the study’s screening process.
Fig. 2
Fig. 3: Effectiveness of vitamin E and placebo in the comparison of signs in patients with RA.
Fig. 4

Data availability

The datasets created and/or analyzed during this work may be found in Pubmed, Web of Science, Cochrane Library, and Embase.


  1. Mcinnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis[J]. Lancet. 2017;389:2328–37.

    CAS  PubMed  Article  Google Scholar 

  2. England BR, Thiele GM, Anderson DR, Mikuls TR. Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications[J]. Bmj. 2018;361:k1036.

    PubMed  PubMed Central  Article  Google Scholar 

  3. Khansari N, Shakiba Y, Mahmoudi M. Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer[J]. Recent Pat Inflamm Allergy Drug Disco. 2009;3:73–80.

    CAS  Article  Google Scholar 

  4. Medzhitov R. Origin and physiological roles of inflammation[J]. Nature. 2008;454:428–35.

    CAS  PubMed  Article  Google Scholar 

  5. Wójcik P, Gęgotek A, Žarković N, Skrzydlewska E. Oxidative stress and lipid mediators modulate immune cell functions in autoimmune diseases[J]. Int J Mol Sci 2021;22:723.

  6. Steinz MM, Santos-Alves E, Lanner JT. Skeletal muscle redox signaling in rheumatoid arthritis[J]. Clin Sci (Lond). 2020;134:2835–50.

    CAS  Article  Google Scholar 

  7. Lanas A. A review of the gastrointestinal safety data-a gastroenterologist’s perspective[J]. Rheumatol (Oxf). 2010;49:ii3–10. Suppl 2

    CAS  Article  Google Scholar 

  8. Okoro CA, Zhao G, Li C, Balluz LS. Has the use of complementary and alternative medicine therapies by U.S. adults with chronic disease-related functional limitations changed from 2002 to 2007?[J]. J Alter Complement Med. 2013;19:217–23.

    Article  Google Scholar 

  9. Malekahmadi M, Moradi Moghaddam O, Islam SMS, Tanha K, Nematy M, Pahlavani N, et al. Evaluation of the effects of pycnogenol (French maritime pine bark extract) supplementation on inflammatory biomarkers and nutritional and clinical status in traumatic brain injury patients in an intensive care unit: A randomized clinical trial protocol[J]. Trials. 2020;21:162.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. Kolahdouz-Mohammadi R, Malekahmadi M, Clayton ZS, Sadat SZ, Pahlavani N, Sikaroudi MK, et al. Effect of egg consumption on blood pressure: a systematic review and meta-analysis of randomized clinical trials[J]. Curr Hypertens Rep. 2020;22:24.

    PubMed  PubMed Central  Article  Google Scholar 

  11. Mansouri M, Pahlavani N, Sharifi F, Varmaghani M, Shokri A, Yaghubi H, et al. Dairy consumption in relation to hypertension among a large population of university students: the MEPHASOUS study[J]. Diabetes Metab Syndr Obes. 2020;13:1633–42.

    PubMed  PubMed Central  Article  Google Scholar 

  12. Movahed S, Varshoee Tabrizi F, Pahlavani N, Seilanian Toussi M, Motlagh A, Eslami S, et al. Comprehensive assessment of nutritional status and nutritional-related complications in newly diagnosed esophageal cancer patients: a cross-sectional study[J]. Clin Nutr. 2021;40:4449–55.

    CAS  PubMed  Article  Google Scholar 

  13. Buch MH. Defining refractory rheumatoid arthritis[J]. Ann Rheum Dis. 2018;77:966–9.

    CAS  PubMed  Article  Google Scholar 

  14. Fernández-Llanio Comella N, Fernández Matilla M, Castellano Cuesta JA. Have complementary therapies demonstrated effectiveness in rheumatoid arthritis?[J]. Reumatol Clin. 2016;12:151–7.

    PubMed  Article  Google Scholar 

  15. Taibi DM, Bourguignon C. The role of complementary and alternative therapies in managing rheumatoid arthritis[J]. Fam Community Health. 2003;26:41–52.

    PubMed  Article  Google Scholar 

  16. Ridgley LA, Anderson AE, Pratt AG. What are the dominant cytokines in early rheumatoid arthritis?[J]. Curr Opin Rheumatol. 2018;30:207–14.

    CAS  PubMed  Article  Google Scholar 

  17. Pisetsky DS. Advances in the treatment of rheumatoid arthritis: costs and challenges[J]. N. C Med J. 2017;78:337–40.

    PubMed  Google Scholar 

  18. Evangelatos G, Fragoulis GE, Koulouri V, Lambrou GI. MicroRNAs in rheumatoid arthritis: from pathogenesis to clinical impact[J]. Autoimmun Rev. 2019;18:102391.

    CAS  PubMed  Article  Google Scholar 

  19. Kolarz B, Podgorska D, Podgorski R. Insights of rheumatoid arthritis biomarkers[J]. Biomarkers. 2021;26:185–95.

    CAS  PubMed  Article  Google Scholar 

  20. Forsyth C, Kouvari M, D’cunha NM, Georgousopoulou EN, Panagiotakos DB, Mellor DD, et al. The effects of the Mediterranean diet on rheumatoid arthritis prevention and treatment: a systematic review of human prospective studies[J]. Rheumatol Int. 2018;38:737–47.

    PubMed  Article  Google Scholar 

  21. Aletaha D. Precision medicine and management of rheumatoid arthritis[J]. J Autoimmun. 2020;110:102405.

    CAS  PubMed  Article  Google Scholar 

  22. Philippou E, Petersson SD, Rodomar C, Nikiphorou E. Rheumatoid arthritis and dietary interventions: systematic review of clinical trials[J]. Nutr Rev. 2021;79:410–28.

    PubMed  Article  Google Scholar 

  23. Kim KW, Kim BM, Won JY, Min HK, Lee SJ, Lee SH, et al. Tocotrienol regulates osteoclastogenesis in rheumatoid arthritis[J]. Korean J Intern Med. 2021;36:S273–s282.

    CAS  PubMed  Article  Google Scholar 

  24. Dai W, Qi C, Wang S. Synergistic effect of glucosamine and vitamin E against experimental rheumatoid arthritis in neonatal rats[J]. Biomed Pharmacother. 2018;105:835–40.

    CAS  PubMed  Article  Google Scholar 

  25. Willers J, Fasse S, Putschky N, Zeidler H, Pott HG, Bernateck M, et al. Combined add-on supplementation of omega-3 fatty acids, vitamin E, vitamin A, copper, and selenium in rheumatoid arthritis[J]. Food Nutr Sci. 2011;2:714–23.

    CAS  Google Scholar 

  26. Aryaeian N, Shahram F, Djalali M, Eshragian MR, Djazayeri A, Sarrafnejad A, et al. Effect of conjugated linoleic acid, vitamin E and their combination on lipid profiles and blood pressure of Iranian adults with active rheumatoid arthritis[J]. Vasc health risk Manag. 2008;4:1423–32.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. Aryaeian N, Djalali M, Shahram F, Djazayery A, Eshragian MR. Effect of conjugated linoleic acid, vitamin E, alone or combined on immunity and inflammatory parameters in adults with active rheumatoid arthritis: a randomized controlled trial[J]. Int J Preventive Med. 2014;5:1567–77.

    Google Scholar 

  28. Aryaeian N, Shahram F, Djalali M, Eshragian MR, Djazayeri A, Sarrafnejad A, et al. Effect of conjugated linoleic acids, vitamin E and their combination on the clinical outcome of Iranian adults with active rheumatoid arthritis[J]. Int J Rheum Dis. 2009;12:20–28.

    PubMed  Article  Google Scholar 

  29. Sangeetha CD, Vasanthi B, Porkodi R, Komathi J. Effect of vitamin E supplementation in rheumatoid arthritis - a case control study[J]. Int J Pharm Biol Arch. 2014;5:60–65.

    Google Scholar 

  30. Vaidya B, Bhochhibhoya M, Nakarmi S. Efficacy of vitamin E in methotrexate-induced hepatotoxicity in rheumatoid arthritis: an open-label case-control study[J]. Int J Rheumatol. 2020;2020:5723485.

  31. Edmonds SE, Winyard PG, Guo R, Kidd B, Merry P, Langrish-Smith A, et al. Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial[J]. Ann Rheum Dis. 1997;56:649–55.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. Karlson EW, Shadick NA, Cook NR, Buring JE, Lee IM. Vitamin E in the primary prevention of rheumatoid arthritis: the women’s health study[J]. Arthritis Care Res. 2008;59:1589–95.

    CAS  Article  Google Scholar 

  33. Tulleken JE, Limburg PC, Muskiet FAJ, Van Rijswijk MH. Vitamin E status during dietary fish oil supplementation in rheumatoid arthritis[J]. Arthritis Rheumatism. 1990;33:1416–9.

    CAS  PubMed  Article  Google Scholar 

  34. Van Der Woude D, Van Der Helm-Van Mil AHM. Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis[J]. Best Pr Res Clin Rheumatol. 2018;32:174–87.

    Article  Google Scholar 

  35. Filippucci E, Cipolletta E, Mashadi Mirza R, Carotti M, Giovagnoni A, Salaffi F, et al. Ultrasound imaging in rheumatoid arthritis[J]. Radio Med. 2019;124:1087–1100.

    Article  Google Scholar 

  36. Karami J, Aslani S, Jamshidi A, Garshasbi M, Mahmoudi M. Genetic implications in the pathogenesis of rheumatoid arthritis; an updated review[J]. Gene. 2019;702:8–16.

    CAS  PubMed  Article  Google Scholar 

  37. Polyakova YV, Zavodovsky BV, Sivordova LE, Akhverdyan YR. Zborovskaya I A. Visfatin and rheumatoid arthritis: pathogenetic implications and clinical utility[J]. Curr Rheumatol Rev. 2020;16:224–39.

    CAS  PubMed  Article  Google Scholar 

  38. Shabgah AG, Norouzi F, Hedayati-Moghadam M, Soleimani D, Pahlavani N, Navashenaq JG. A comprehensive review of long non-coding RNAs in the pathogenesis and development of non-alcoholic fatty liver disease[J]. Nutr Metab (Lond). 2021;18:22.

    CAS  Article  Google Scholar 

  39. Gowhari Shabgah A, Hejri Zarifi S, Mazloumi Kiapey SS, Ezzatifar F, Pahlavani N, Soleimani D, et al. Curcumin and cancer; are long non-coding RNAs missing link?[J]. Prog Biophys Mol Biol. 2021;164:63–71.

    CAS  PubMed  Article  Google Scholar 

  40. Wang J, Yan S, Yang J, Lu H, Xu D, Wang Z. Non-coding RNAs in rheumatoid arthritis: from bench to bedside[J]. Front Immunol. 2019;10:3129.

    CAS  PubMed  Article  Google Scholar 

  41. Ayachit G, Shaikh I, Sharma P, Jani B, Shukla L, Sharma P, et al. De novo transcriptome of Gymnema sylvestre identified putative lncRNA and genes regulating terpenoid biosynthesis pathway[J]. Sci Rep. 2019;9:14876.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  42. Liu W, Sheng L, Nie L, Wen X, Mo X. Functional interaction between long non-coding RNA and microRNA in rheumatoid arthritis[J]. J Clin Lab Anal. 2020;34:e23489.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Maeda Y, Takeda K. Host-microbiota interactions in rheumatoid arthritis[J]. Exp Mol Med. 2019;51:1–6.

    CAS  PubMed  Article  Google Scholar 

  44. Xu H, Zhao H, Fan D, Liu M, Cao J, Xia Y, et al. Interactions between gut microbiota and immunomodulatory cells in rheumatoid arthritis[J]. Mediators Inflamm. 2020;2020:1430605.

    PubMed  PubMed Central  Google Scholar 

  45. Rosser EC, Piper CJM, Matei DE, Blair PA, Rendeiro AF, Orford M. et al. Microbiota-derived metabolites suppress arthritis by amplifying Aryl-hydrocarbon receptor activation in regulatory B cells[J]. Cell Metab. 2020;31:837–51.e10.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. Choi Y, Lee S, Kim S, Lee J, Ha J, Oh H, et al. Vitamin E (α-tocopherol) consumption influences gut microbiota composition[J]. Int J Food Sci Nutr. 2020;71:221–5.

    CAS  PubMed  Article  Google Scholar 

  47. Liu KY, Nakatsu CH, Jones-Hall Y, Kozik A, Jiang Q. Vitamin E alpha- and gamma-tocopherol mitigate colitis, protect intestinal barrier function and modulate the gut microbiota in mice[J]. Free Radic Biol Med. 2021;163:180–9.

    CAS  PubMed  Article  Google Scholar 

  48. Jiang Q. Metabolism of natural forms of vitamin E and biological actions of vitamin E metabolites[J]. Free Radic Biol Med. 2022;179:375–87.

    CAS  PubMed  Article  Google Scholar 

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We gratefully acknowledge ms. Weijing Fan. She is thanked for her silent support and advice to the first author. We are very grateful for her help with different aspects of the study. Thanks also to her for her assistance in preparing this manuscript. We hope ms. Weijin Fan will marry the first author.


This study was supported by funding from the Natural Science Foundation of Shaanxi Province (No. 2021JM569, No. 2018JM7081).

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All authors read and approved the final manuscript. And all authors discuss the concept of the manuscript. Conception or design of the work: RZ and JM. Contributed equally to this study. HK and RZ: carried out the literature search and statistical analysis; collected, analyzed, and interpreted the data. HK: drafting the article; JM: wrote and critically revised the manuscript.

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Correspondence to Rui Zhang or Jianbing Ma.

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Kou, H., Qing, Z., Guo, H. et al. Effect of vitamin E supplementation in rheumatoid arthritis: a systematic review and meta-analysis. Eur J Clin Nutr (2022).

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