Skip to main content

Advertisement

SpringerLink
Log in

Anemia, serum vitamin B12, and folic acid in patients with rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Objective

Although anemia is frequent in inflammatory rheumatic diseases, data regarding vitamin B12 status is scarce. The purpose of this study was to analyze the incidence and nature of B12 and folic acid (FA) deficiencies in a cohort of rheumatic patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and systemic lupus erythematosus (SLE).

Methods

Levels of B12, FA, and parameters of anemia were recovered or examined in 276 outpatients. In those with recent findings of low serum B12 levels, further studies of serum homocysteine (Hcy) and urine methylmalonic acid (MMA) levels were performed.

Results

The incidence of anemia was high: 49%, 46%, and 35%, in RA, SLE, and PsA, respectively. Low levels of serum B12 were also frequent (24%), with almost similar occurrence in the three disease groups. Deficiency in FA was rare (<5%). Mean levels of both vitamins did not differ significantly among the three groups. No correlation between serum B12 levels and anemia was found. In the 15 patients with recently detected low B12 levels, Hcy and MMA were evaluated before and following B12 therapy. In ten of them, baseline Hcy levels were high, while MMA was increased in one patient only. Response to B12 administration, i.e., a decrease in Hcy and/or MMA levels, was noticed in four patients only, suggesting that only 26% of the low-serum-B12 patients had true B12 deficiency.

Conclusions

The incidences of anemia and decreased serum B12 levels were high in these three groups of rheumatic patients. However, true tissue deficiency seems to be much rarer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Vreugdenhil G, Lindemans J, Eijk HG van, Swaak AJ (1992) Elevated serum transcobalamin levels in anaemia of rheumatoid arthritis: correlation with disease activity but not with serum tumour necrosis factor alpha and interleukin 6. J Intern Med 231:547–550

    CAS  PubMed  Google Scholar 

  2. Vreugdenhil G, Wognum AW, Eijk HG van, Swaak AJ (1990) Anaemia in rheumatoid arthritis: the role of iron, vitamin B12, and folic acid deficiency, and erythropoietin responsiveness. Ann Rheum Dis 49:93–98

    CAS  PubMed  Google Scholar 

  3. Pettersson T, Friman C, Abrahamsson L, Nilsson B, Norberg B (1998) Serum homocysteine and methylmalonic acid in patients with rheumatoid arthritis and cobalaminopenia. J Rheumatol 25:859–863

    CAS  PubMed  Google Scholar 

  4. Grindulis KA, Calverley M, Cox C (1984) Rheumatoid arthritis: is serum vitamin B12 high in active disease? J Rheumatol 11:211–212

    Google Scholar 

  5. Roubenoff R, Roubenoff RA, Selhub J, Nadeau MR, Cannon JG, Freeman LM, Dinarello CA, Resenberg IH (1995) Abnormal vitamin B6 status in rheumatoid cachexia. Association with spontaneous tumor necrosis factor alpha production and markers of inflammation. Arthritis Rheum 38:105–109

    CAS  PubMed  Google Scholar 

  6. Giordano N, Cecconami L, Marcucci P, Battisti E, Magaro L, Morozzi G, Mariano A, Marcolongo R (1992) The role of iron, vitamin B12, folic acid and erythropoietin in the anemia of rheumatoid arthritis. Clin Exp Rheumatol 10:201–202

    CAS  PubMed  Google Scholar 

  7. Dyer NH, Kendall MJ, Hawkins CF (1971) Malabsorption in rheumatoid disease. Ann Rheum Dis 30:626–630

    CAS  PubMed  Google Scholar 

  8. Benn HP, Drews J, Randzio G, Jensen JM, Loffler H (1988) Does active rheumatoid arthritis affect intestinal iron absorption? Ann Rheum Dis 47:144–149

    Google Scholar 

  9. Petri M, Roubenoff R, Dallal GE, Nadeau MR, Selhub J, Rosenberg IH (1996) Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus. Lancet 348:1120–1124

    Article  CAS  PubMed  Google Scholar 

  10. Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, Spitz PW, Haga M, Kleinheksel SM, Cathey MA (1994) The mortality of rheumatoid arthritis. Arthritis Rheum 37:481–494

    CAS  PubMed  Google Scholar 

  11. Roubenoff R, Dellaripa P, Nadeau MR, Abad LW, Muldoon BA, Selhub J, Rosenberg IH (1997) Abnormal homocysteine metabolism in rheumatoid arthritis. Arthritis Rheum 40:718–722

    CAS  PubMed  Google Scholar 

  12. Hernanz A, Plaza A, Martin-Mola, De Miguel E (1999) Increased plasma levels of homocysteine and other thiol compounds in rheumatoid arthritis women. Clin Biochem 32:65–70

    Article  CAS  PubMed  Google Scholar 

  13. Graham IM, Daly LE, Refsum HM (1997) Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 277:1775–1781

    CAS  PubMed  Google Scholar 

  14. Jacobsen DW (1998) Homocysteine and vitamins in cardiovascular disease. Clin Chem 44:1833–1843

    CAS  PubMed  Google Scholar 

  15. Pancharuniti N, Lewis CA, Sauberlich HE, Perkins LL, Go RC, Alvarez JO, Macaluso M, Acton RT, Copeland RB, Cousins AL (1994) Plasma homocysteine, folate, and vitamin B-12 concentrations and risk for early-onset coronary artery disease. Am J Clin Nutr 59:940–948

    CAS  PubMed  Google Scholar 

  16. Klee GG (2000) Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs. vitamin B12 and folate. Clin Chem 46:1277–1283

    CAS  PubMed  Google Scholar 

  17. Jacobsen DW, Gatautis VJ, Green R, (1994) Rapid HPLC determination of total homocysteine and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy subjects. Clin Chem 40:873–881

    CAS  PubMed  Google Scholar 

  18. Leeb BF, Witzmann G, Ogris E, Studnicka-Benke A, Andel I, Schweitzer H, Smollen JS (1995) Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose methotrexate therapy of rheumatoid arthritis psoriatic arthritis patients. Clin Exp Rheumatol 13:459–463

    CAS  PubMed  Google Scholar 

  19. Ede AE van, Laan RFJM, Blom HJ, Boers GHJ, Haagsma CJ, Thomas CMG, Boo TM de, Putte LBA van de (2002) Homocysteine and folate in methotrexate-treated patients with rheumatoid arthritis. Rheumatology 41:658–665

    Article  PubMed  Google Scholar 

  20. Arthritis and allied conditions (1996) In: Koopman WJ (ed) A textbook of rheumatology. Williams and Wilkins, Baltimore

  21. Stabler SP, Marcell PD, Podell EV (1986) Assay of methyl malonic acid in serum of patients with cobalamin deficiency using capillary gas chromatography mass spectrometry. J Clin Invest 77:1606–1612

    CAS  PubMed  Google Scholar 

  22. Haagsma CJ, Blom HJ, Riel PLCM van, Hof MA van't, Giesendorf BAJ, Oppenraaij-Emmerzaal D van, Putte LBA van de (1999) Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Ann Rheum Dis 58:79–84

    CAS  PubMed  Google Scholar 

  23. Yao Y, Yao SL, Yao SS, Yao G, Lou W (1992) Prevalence of vitamin B12 deficiency among geriatric outpatients. J Fam Pract 35:524–525

    CAS  PubMed  Google Scholar 

  24. Jensen OK, Rasmussen C, Mollerup F, Christensen PB, Hansen H, Ekelund S, Thulstrup AM (2002). Hyperhomocysteinemia in rheumatoid arthritis: influence of methotrexate treatment and folic acid supplementation. J Rheumatol 29:1615–1618

    CAS  PubMed  Google Scholar 

  25. Dharmarajan TS, Norkus EP (2001). Approaches to vitamin B12 deficiency. Early treatment may prevent devastating complications. Postgraduate Med 110:99–105

    CAS  Google Scholar 

  26. Carmel R (1990). Subtle and atypical cobalamin deficiency states. Am J Hematol 34:108–114

    CAS  PubMed  Google Scholar 

  27. Lindenbaum J, Healton EB, Savage DG, Brust JC, Garett TJ, Podell ER, Marcell PD, Stabler SP, Allen RH (1988). Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 318:1720–1728

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Geriatrics, Shmuel-Harofeh Geriatric Medical Center, Baer Yaakov, Israel

    Refael Segal, Yehuda Baumoehl, Beni Habot & Arthur Leibovitz

  2. Rheumatology Department, Sourasky Medical Center, Tel Aviv, Israel

    Ori Elkayam, David Levartovsky, Irena Litinsky, Daphna Paran, Irena Wigler & Dan Caspi

  3. Department of Chemistry, Sheba Medical Center, Tel Hashomer, Israel

    Ben Ami Sela

  4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Refael Segal, Yehuda Baumoehl, Ori Elkayam, David Levartovsky, Irena Litinsky, Daphna Paran, Irena Wigler, Beni Habot, Arthur Leibovitz, Ben Ami Sela & Dan Caspi

Authors
  1. Refael Segal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yehuda Baumoehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ori Elkayam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David Levartovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Irena Litinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daphna Paran
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Irena Wigler
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Beni Habot
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Arthur Leibovitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ben Ami Sela
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Dan Caspi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Refael Segal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Segal, R., Baumoehl, Y., Elkayam, O. et al. Anemia, serum vitamin B12, and folic acid in patients with rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus. Rheumatol Int 24, 14–19 (2004). https://doi.org/10.1007/s00296-003-0323-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-003-0323-2

Keywords

Search

Navigation