Clinical Rheumatology

, Volume 31, Issue 12, pp 1733–1739 | Cite as

Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis

  • Gwan Gyu Song
  • Sang-Cheol Bae
  • Young Ho LeeEmail author
Brief Report


The aim of this study was to summarize published results on the association between vitamin D intake and the development of rheumatoid arthritis (RA) and between serum vitamin D levels and RA activity. Evidence of a relationship between vitamin D intake and the development of RA and between serum vitamin D levels and RA activity was studied by summarizing published results using a meta-analysis approach. Three cohort studies including 215,757 participants and 874 incident cases of RA were considered in this meta-analysis, and eight studies on the association between serum vitamin D levels and RA activity involving 2,885 RA patients and 1,084 controls were included. Meta-analysis showed an association between total vitamin D intake and RA incidence (relative risk (RR) of the highest vs. the lowest group = 0.758, 95 % confidence interval (CI) 0.577–0.937, p = 0.047), without between-study heterogeneity (I 2 = 0 %, p = 0.595). Individuals in the highest group for total vitamin D intake were found to have a 24.2 % lower risk of developing RA than those in the lowest group. Subgroup meta-analysis also showed a significant association between vitamin D supplement intake and RA incidence (RR 0.764, 95 % CI 0.628–0.930, p = 0.007), without between-study heterogeneity. All studies, except for one, found that vitamin D levels are inversely associated with RA activity. One study found no correlation between vitamin D levels and disease activity among 85 RA patients, but these patients had a high incidence of vitamin D deficiency, which might have influenced the study outcome. Meta-analysis of 215,757 participants suggests that low vitamin D intake is associated with an elevated risk of RA development. Furthermore, available evidence indicates that vitamin D level is associated with RA activity.


Activity Rheumatoid arthritis Susceptibility Vitamin D 



This study was supported by a grant from the Korean Healthcare Technology R&D Project, Korean Ministry of Health and Welfare (A102065).




  1. 1.
    Harris ED Jr (1990) Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med 322:1277–1289PubMedCrossRefGoogle Scholar
  2. 2.
    Kim HR, Park MK, Cho ML et al (2010) Induction of macrophage migration inhibitory factor in ConA-stimulated rheumatoid arthritis synovial fibroblasts through the P38 map kinase-dependent signaling pathway. Korean J Intern Med 25:317–326PubMedCrossRefGoogle Scholar
  3. 3.
    Cantorna MT (2000) Vitamin D and autoimmunity: is vitamin D status an environmental factor affecting autoimmune disease prevalence? Proc Soc Exp Biol Med 223:230–233PubMedCrossRefGoogle Scholar
  4. 4.
    Maruotti N, Cantatore FP (2010) Vitamin D and the immune system. J Rheumatol 37:491–495PubMedCrossRefGoogle Scholar
  5. 5.
    Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O’garra A (2001) 1alpha,25-Dihydroxyvitamin D3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 167:4974–4980PubMedGoogle Scholar
  6. 6.
    Koizumi T, Nakao Y, Matsui T et al (1985) Effects of corticosteroid and 1,24R-dihydroxy-vitamin D3 administration on lymphoproliferation and autoimmune disease in MRL/MP-lpr/lpr mice. Int Arch Allergy Appl Immunol 77:396–404PubMedCrossRefGoogle Scholar
  7. 7.
    Kamen D, Aranow C (2008) Vitamin D in systemic lupus erythematosus. Curr Opin Rheumatol 20:532–537PubMedCrossRefGoogle Scholar
  8. 8.
    Cutolo M, Otsa K, Paolino S, Yprus M, Veldi T, Seriolo B (2009) Vitamin D involvement in rheumatoid arthritis and systemic lupus erythaematosus. Ann Rheum Dis 68:446–447PubMedCrossRefGoogle Scholar
  9. 9.
    Wen H, Baker JF (2011) Vitamin D, immunoregulation, and rheumatoid arthritis. J Clin Rheumatol 17:102–107PubMedGoogle Scholar
  10. 10.
    Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2011) Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep 38:3643–3651PubMedCrossRefGoogle Scholar
  11. 11.
    Costenbader KH, Feskanich D, Holmes M, Karlson EW, Benito-Garcia E (2008) Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women. Ann Rheum Dis 67:530–535PubMedCrossRefGoogle Scholar
  12. 12.
    Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG (2004) Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum 50:72–77PubMedCrossRefGoogle Scholar
  13. 13.
    Rossini M, Maddali Bongi S, La Montagna G et al (2010) Vitamin D deficiency in rheumatoid arthritis: prevalence, determinants and associations with disease activity and disability. Arthritis Res Ther 12:R216PubMedCrossRefGoogle Scholar
  14. 14.
    Welsh P, Peters MJ, Mcinnes IB et al (2011) Vitamin D deficiency is common in patients with RA and linked to disease activity, but circulating levels are unaffected by TNFalpha blockade: results from a prospective cohort study. Ann Rheum Dis 70:1165–1167PubMedCrossRefGoogle Scholar
  15. 15.
    Braun-Moscovici Y, Toledano K, Markovits D, Rozin A, Nahir AM, Balbir-Gurman A (2011) Vitamin D level: is it related to disease activity in inflammatory joint disease? Rheumatol Int 31:493–499PubMedCrossRefGoogle Scholar
  16. 16.
    Craig SM, Yu F, Curtis JR et al (2010) Vitamin D status and its associations with disease activity and severity in African Americans with recent-onset rheumatoid arthritis. J Rheumatol 37:275–281PubMedCrossRefGoogle Scholar
  17. 17.
    Haque UJ, Bartlett SJ (2010) Relationships among vitamin D, disease activity, pain and disability in rheumatoid arthritis. Clin Exp Rheumatol 28:745–747PubMedGoogle Scholar
  18. 18.
    Kerr GS, Sabahi I, Richards JS et al (2011) Prevalence of vitamin D insufficiency/deficiency in rheumatoid arthritis and associations with disease severity and activity. J Rheumatol 38:53–59PubMedCrossRefGoogle Scholar
  19. 19.
    Cutolo M, Otsa K, Laas K et al (2006) Circannual vitamin d serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe. Clin Exp Rheumatol 24:702–704PubMedGoogle Scholar
  20. 20.
    Kröger H, Penttilä IM, Alhava EM (1993) Low serum vitamin D metabolites in women with rheumatoid arthritis. Scand J Rheumatol 22:172–177PubMedCrossRefGoogle Scholar
  21. 21.
    Lee YH, Rho YH, Choi SJ, Ji JD, Song GG (2006) Association of TNF-alpha-308G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis. Rheumatol Int 27:157–161PubMedCrossRefGoogle Scholar
  22. 22.
    Choi SJ, Rho YH, Ji JD, Song GG (2006) LEE YH: Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford) 45:166–170CrossRefGoogle Scholar
  23. 23.
    Davey P, Grainger D, Macmillan J, Rajan N, Aristides M, Gliksman M (1997) Clinical outcomes with insulin lispro compared with human regular insulin: a meta-analysis. Clin Ther 19:656–674PubMedCrossRefGoogle Scholar
  24. 24.
    Dersimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  25. 25.
    Jadad AR, Moore RA, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12PubMedCrossRefGoogle Scholar
  26. 26.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558PubMedCrossRefGoogle Scholar
  27. 27.
    Cantorna MT, Hayes CE, Deluca HF (1998) 1,25-Dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. J Nutr 128:68–72PubMedGoogle Scholar
  28. 28.
    Szodoray P, Nakken B, Gaal J et al (2008) The complex role of vitamin D in autoimmune diseases. Scand J Immunol 68:261–269PubMedCrossRefGoogle Scholar
  29. 29.
    Cutolo M, Plebani M, Shoenfeld Y, Adorini L, Tincani A (2011) Vitamin D endocrine system and the immune response in rheumatic diseases. Vitam Horm 86:327–351PubMedCrossRefGoogle Scholar
  30. 30.
    Linker-Israeli M, Elstner E, Klinenberg JR, Wallace DJ, Koeffler HP (2001) Vitamin D(3) and its synthetic analogs inhibit the spontaneous in vitro immunoglobulin production by SLE-derived PBMC. Clin Immunol 99:82–93PubMedCrossRefGoogle Scholar
  31. 31.
    Derdemezis CS, Voulgari PV, Drosos AA, Kiortsis DN (2011) Obesity, adipose tissue and rheumatoid arthritis: coincidence or more complex relationship? Clin Exp Rheumatol 29:712–27Google Scholar
  32. 32.
    Awad AB, Alappat L, Valerio M (2012) Vitamin D and metabolic syndrome risk factors: evidence and mechanisms. Crit Rev Food Sci Nutr 52:103–12Google Scholar
  33. 33.
    Cutolo M, Otsa K, Uprus M, Paolino S, Seriolo B (2007) Vitamin D in rheumatoid arthritis. Autoimmun Rev 7:59–64PubMedCrossRefGoogle Scholar
  34. 34.
    van der Veen MJ, Bijlsma JW (1992) Effects of different regimes of corticosteroid treatment on calcium and bone metabolism in rheumatoid arthritis. Clin Rheumatol 11:388–392PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2012

Authors and Affiliations

  1. 1.Division of Rheumatology, Department of Internal Medicine, Korea University Anam HospitalKorea University College of MedicineSeoulSouth Korea
  2. 2.The Hospital for Rheumatic DiseasesHanyang University Medical CenterSeoulKorea

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