Skip to main content

Restless legs syndrome is a relevant comorbidity in patients with inflammatory bowel disease


Background and aims

In patients with inflammatory bowel disease (IBD), restless legs syndrome (RLS) may occur as an extraintestinal disease manifestation. Iron deficiency (ID) or folate deficiency/vitamin B12 deficiency (FD/VB12D) has previously been described to cause RLS. Here, we determined the prevalence and severity of RLS in IBD patients and evaluated the effect of iron and/or folic acid/vitamin B12 supplementation.


Patients were screened for ID and RLS by a gastroenterologist. If RLS was suspected, a neurologist was consulted for definitive diagnosis and severity. Patients with RLS and ID, FD, or VB12D received supplementation and were followed-up at weeks 4 and 11 after starting supplementation.


A total of 353 IBD patients were included. Prevalence for RLS was 9.4% in Crohn’s disease (CD) and 8% in ulcerative colitis (UC). Prevalence for the subgroup of clinically relevant RLS (symptoms ≥ twice/week with at least moderate distress) was 7.1% (n = 16) for CD and 4.8% (n = 6) for UC. 38.7% of RLS patients presented with ID, FD, and/or VB12D. Most frequently ID was seen (25.8%; n = 8). Iron supplementation resulted in RLS improvement (p = 0.029) at week 4 in seven out of eight patients.


Although the overall prevalence of RLS in IBD did not differ to the general population, clinically relevant RLS was more frequent in IBD patients and, therefore, it is important for clinicians to be aware of RLS symptoms. Though for definite diagnosis and proper treatment of RLS, a neurologist must be consulted. Additionally, iron supplementation of IBD patients with ID can improve RLS symptoms.

Trial registration No. NCT03457571

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. Repiso A, Alcántara M, Muñoz-Rosas C et al (2006) Extraintestinal manifestations of Crohn’s disease: prevalence and related factors. Rev Esp Enferm Dig 98:510–517

    Article  PubMed  CAS  Google Scholar 

  2. Ferro JM, Oliveira SN, Correia L (2014) Chapter 40—Neurologic manifestations of inflammatory bowel diseases. In: Biller J, Ferro JM (eds) Handbook of clinical neurology, vol 120. Neurologic aspects of systemic disease part II. Elsevier, Amsterdam, pp 595–605. Available at: Accessed 18 Feb 2016

  3. Guagnozzi D, Lucendo AJ (2014) Anemia in inflammatory bowel disease: a neglected issue with relevant effects. World J Gastroenterol: WJG 20:3542–3551

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Allen RP, Earley CJ (2007) The role of iron in restless legs syndrome. Mov Disord 22(Suppl 1):S440–S448

    Article  PubMed  Google Scholar 

  5. Weinstock LB, Bosworth BP, Scherl EJ, Li E, Iroku U, Munsell MA, Mullen GE, Walters AS (2010) Crohn’s disease is associated with restless legs syndrome. Inflamm Bowel Dis 16:275–279 Available at: Accessed 29 May 2015

    Article  PubMed  Google Scholar 

  6. Takahara I, Takeshima F, Ichikawa T, Matsuzaki T, Shibata H, Miuma S, Akazawa Y, Miyaaki H, Taura N, Nakao K (2017) Prevalence of restless legs syndrome in patients with inflammatory bowel disease. Dig Dis Sci 62:761–767

    Article  PubMed  Google Scholar 

  7. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB, International Restless Legs Syndrome Study Group (2014) Restless legs syndrome/Willis–Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria—history, rationale, description, and significance. Sleep Med 15:860–873

    Article  PubMed  Google Scholar 

  8. Whittom S, Dauvilliers Y, Pennestri M-H, Vercauteren F, Molinari N, Petit D, Montplaisir J (2007) Age-at-onset in restless legs syndrome: a clinical and polysomnographic study. Sleep Med 9:54–59

    Article  PubMed  CAS  Google Scholar 

  9. Dauvilliers Y, Winkelmann J (2013) Restless legs syndrome: update on pathogenesis. Curr Opin Pulm Med 19:594–600

    Article  PubMed  CAS  Google Scholar 

  10. Winkelmann J, Wetter TC, Collado-Seidel V, Gasser T, Dichgans M, Yassouridis A, Trenkwalder C (2000) Clinical characteristics and frequency of the hereditary restless legs syndrome in a population of 300 patients. Sleep 23:597–602

    Article  PubMed  CAS  Google Scholar 

  11. Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, Jalilzadeh S, Fulda S, Pütz B, Eckstein G, Hauk S, Trenkwalder C, Zimprich A, Stiasny-Kolster K, Oertel W, Bachmann CG, Paulus W, Peglau I, Eisensehr I, Montplaisir J, Turecki G, Rouleau G, Gieger C, Illig T, Wichmann HE, Holsboer F, Müller-Myhsok B, Meitinger T (2007) Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 39:1000–1006

    Article  PubMed  CAS  Google Scholar 

  12. Trenkwalder C, Allen R, Högl B, Paulus W, Winkelmann J (2016) Restless legs syndrome associated with major diseases. Neurology 86:1336–1343

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Allen RP, Auerbach S, Bahrain H, Auerbach M, Earley CJ (2013) The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia. Am J Hematol 88:261–264

    Article  PubMed  Google Scholar 

  14. Group TIRLSS (2003) Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 4:121–132

    Article  Google Scholar 

  15. Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, Ferini-Strambi L (2005) Restless legs syndrome prevalence and impact: rest general population study. Arch Intern Med 165:1286–1292

    Article  PubMed  Google Scholar 

  16. Allen RP, Bharmal M, Calloway M (2011) Prevalence and disease burden of primary restless legs syndrome: results of a general population survey in the United States. Mov Disord 26:114–120

    Article  PubMed  Google Scholar 

  17. Ganzoni AM (1970) Intravenous iron-dextran: therapeutic and experimental possibilities. Schweiz Med Wochenschr 100:301–303

    PubMed  CAS  Google Scholar 

  18. Silverberg MS, Satsangi J, Ahmad T, Arnott IDR, Bernstein CN, Brant SR, Caprilli R, Colombel JF, Gasche C, Geboes K, Jewell DP, Karban A, Loftus EV, Peña AS, Riddell RH, Sachar DB, Schreiber S, Steinhart AH, Targan SR, Vermeire S, Warren BF (2005) Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 19(Suppl A):5A–36A

    Article  PubMed  Google Scholar 

  19. Allen RP, La Buda MC, Becker P et al (2002) Family history study of the restless legs syndrome. Sleep Med 3(Supplement):S3–S7

    Article  PubMed  Google Scholar 

  20. Berger K, Luedemann J, Trenkwalder C, John U, Kessler C (2004) SEx and the risk of restless legs syndrome in the general population. Arch Intern Med 164:196–202

    Article  PubMed  Google Scholar 

  21. Ulfberg J, Nyström B, Carter N, Edling C (2001) Prevalence of restless legs syndrome among men aged 18 to 64 years: an association with somatic disease and neuropsychiatric symptoms. Mov Disord 16:1159–1163

    Article  PubMed  CAS  Google Scholar 

  22. Winkelmann J, Ferini-Strambi L (2006) Genetics of restless legs syndrome. Sleep Med Rev 10:179–183

    Article  PubMed  Google Scholar 

  23. Bjorvatn B, Leissner L, Ulfberg J et al (2005) Prevalence, severity and risk factors of restless legs syndrome in the general adult population in two Scandinavian countries. Sleep Med 6:307–312

    Article  PubMed  Google Scholar 

  24. Hoek PD, Smits MG, de Roos NM et al (2015) Increased prevalence of restless legs syndrome in patients with Crohn’s disease. Eur J Gastroenterol Hepatol 27:951–955

    Article  PubMed  Google Scholar 

  25. Picchietti D, Allen RP, Walters AS, Davidson JE, Myers A, Ferini-Strambi L (2007) Restless legs syndrome: prevalence and impact in children and adolescents—the Peds REST Study. Pediatrics 120:253–266

    Article  PubMed  Google Scholar 

  26. Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L (2016) Iron deficiency anaemia. Lancet 387:907–916

    Article  PubMed  CAS  Google Scholar 

  27. Walters AS, Hickey K, Maltzman J, Verrico T, Joseph D, Hening W, Wilson V, Chokroverty S (1996) A questionnaire study of 138 patients with restless legs syndrome: the “Night-Walkers” survey. Neurology 46:92–95

    Article  PubMed  CAS  Google Scholar 

  28. Allen RP, Earley CJ (2000) Defining the phenotype of the restless legs syndrome (RLS) using age-of-symptom-onset. Sleep Med 1:11–19

    Article  PubMed  CAS  Google Scholar 

  29. Trotti LM, Bhadriraju S, Becker LA (2012) Iron for restless legs syndrome. Cochrane Database Syst Rev 5:CD007834

    PubMed Central  Google Scholar 

  30. Sloand JA, Shelly MA, Feigin A, Bernstein P, Monk RD (2004) A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis 43:663–670

    Article  PubMed  CAS  Google Scholar 

  31. Grote L, Leissner L, Hedner J, Ulfberg J (2009) A randomized, double-blind, placebo controlled, multi-center study of intravenous iron sucrose and placebo in the treatment of restless legs syndrome. Mov Disord 24:1445–1452

    Article  PubMed  Google Scholar 

  32. Wang J, O’Reilly B, Venkataraman R, Mysliwiec V, Mysliwiec A (2009) Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: a randomized, double-blind, placebo-controlled study. Sleep Med 10:973–975

    Article  PubMed  Google Scholar 

  33. Schindlbeck KA, Becker J, Berger F et al (2016) Impact of restless legs syndrome in patients with inflammatory bowel disease on sleep, fatigue, and quality of life. Int J Color Dis:1–6

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Jochen Maul.

Ethics declarations

The study was approved (16 January 2014) by the ethics committee of the Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin (reference EA4/132/13).

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material


(DOCX 41 kb)


(DOCX 14 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Becker, J., Berger, F., Schindlbeck, K.A. et al. Restless legs syndrome is a relevant comorbidity in patients with inflammatory bowel disease. Int J Colorectal Dis 33, 955–962 (2018).

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Restless legs syndrome
  • Inflammatory bowel disease
  • Iron deficiency
  • Crohn’s disease
  • Ulcerative colitis