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

Abstract

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.

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References

  1. 1.

    Harris ED Jr (1990) Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med 322:1277–1289

    PubMed  Article  Google 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 25:317–326

    PubMed  Article  Google 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 223:230–233

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Maruotti N, Cantatore FP (2010) Vitamin D and the immune system. J Rheumatol 37:491–495

    PubMed  Article  CAS  Google 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 167:4974–4980

    PubMed  CAS  Google 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 77:396–404

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Kamen D, Aranow C (2008) Vitamin D in systemic lupus erythematosus. Curr Opin Rheumatol 20:532–537

    PubMed  Article  CAS  Google 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 68:446–447

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Wen H, Baker JF (2011) Vitamin D, immunoregulation, and rheumatoid arthritis. J Clin Rheumatol 17:102–107

    PubMed  Google 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 38:3643–3651

    PubMed  Article  CAS  Google 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 67:530–535

    PubMed  Article  CAS  Google 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 50:72–77

    PubMed  Article  CAS  Google 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:R216

    PubMed  Article  CAS  Google 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 70:1165–1167

    PubMed  Article  Google 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 31:493–499

    PubMed  Article  CAS  Google 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 37:275–281

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Haque UJ, Bartlett SJ (2010) Relationships among vitamin D, disease activity, pain and disability in rheumatoid arthritis. Clin Exp Rheumatol 28:745–747

    PubMed  CAS  Google 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 38:53–59

    PubMed  Article  Google 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 24:702–704

    PubMed  CAS  Google Scholar 

  20. 20.

    Kröger H, Penttilä IM, Alhava EM (1993) Low serum vitamin D metabolites in women with rheumatoid arthritis. Scand J Rheumatol 22:172–177

    PubMed  Article  Google 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 27:157–161

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Choi SJ, Rho YH, Ji JD, Song GG (2006) LEE YH: Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford) 45:166–170

    Article  CAS  Google 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 19:656–674

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Dersimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    PubMed  Article  CAS  Google 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 17:1–12

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    PubMed  Article  Google 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 128:68–72

    PubMed  CAS  Google Scholar 

  28. 28.

    Szodoray P, Nakken B, Gaal J et al (2008) The complex role of vitamin D in autoimmune diseases. Scand J Immunol 68:261–269

    PubMed  Article  CAS  Google 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 86:327–351

    PubMed  Article  CAS  Google 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 99:82–93

    PubMed  Article  CAS  Google 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 29:712–27

    Google 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 52:103–12

    Google Scholar 

  33. 33.

    Cutolo M, Otsa K, Uprus M, Paolino S, Seriolo B (2007) Vitamin D in rheumatoid arthritis. Autoimmun Rev 7:59–64

    PubMed  Article  CAS  Google 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 11:388–392

    PubMed  Article  Google Scholar 

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Acknowledgments

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

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Correspondence to Young Ho Lee.

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Song, G.G., Bae, SC. & Lee, Y.H. Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis. Clin Rheumatol 31, 1733–1739 (2012). https://doi.org/10.1007/s10067-012-2080-7

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Keywords

  • Activity
  • Rheumatoid arthritis
  • Susceptibility
  • Vitamin D