Prevalence and risk factors for vitamin D deficiency in Crohn disease patients: A Tunisian study


Shema Ayadi
Myriam Ayari
Afef Bahlous
Yosra Zaimi
Emna Bel Hadj Mabrouk
Leila Mouelhi
Radhouane Debbeche


Introduction: Vitamin D plays a role in regulating the immune response through an immunomodulatory effect, and is probably involved in the pathophysiology of Crohn's disease (CD).

Aim: to assess vitamin D status in patients with CD as well as in healthy controls and to determine associated factors of vitamin D deficiency in patients with CD.

Methods: We conducted a prospective study over 18 months, including CD patients with age and sex matched with healthy controls. Suboptimal vitamin D status was defined by vitamin D serum level < 30 ng/ml, vitamin insufficiency by vitamin D serum level between 10 and 30 ng/ml and vitamin deficiency serum level < 10 ng/ml.


Results: We included 77 subjects (52 patients with CD and 25 controls) with mean age of 38 years± 11. Most patients and controls had suboptimal levels of vitamin D (98% and 96% respectively) including vitamin D deficiency in 75% and 67%, respectively and vitamin D insufficiency in 25% and 33%, respectively. In univariate analysis, vitamin D deficiency was associated with disease flare-up (p=0.001), anemia (p=0.002), hypo-albuminemia (p=0.002), elevated C-reactive protein (CRP) (p=0.003), Crohn’s Disease Activity Index (CDAI) (p<0.001), ileal location (p=0.04) and immunosuppressive therapy (p=0.01). In multivariate analysis, only CDAI was significantly associated with vitamin D deficiency (p=0.003, OR=9.33).

Conclusion: Vitamin D deficiency is common in Tunisian CD patients as well as in controls and is associated with disease activity.


Inflammatory bowel diseases, Crohn’s disease, vitamin D



  1. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science 1983 ;221(4616):1181–3.
  2. Mouli VP, Ananthakrishnan AN. Review article: Vitamin D and inflammatory bowel diseases. Aliment Pharmacol Ther 2014;39(2):125‑36.
  3. Dumitrescu G, Mihai C, Dranga M, Prelipcean CC. Serum 25-hydroxyvitamin D concentration and inflammatory bowel disease characteristics in Romania. World J Gastroenterol 2014;20(9):2392‑6.
  4. Butcher RO, Limdi JK. Vitamin D status in Inflammatory Bowel Disease: Are clinicians seeing the light? J Crohns Colitis 2012;6(10):1039‑40.
  5. Mithal A, Wahl DA, Bonjour JP, et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos int 2009;20(11):1807‑20.
  6. Leskovar D, Meštrović T, Barešić A, et al. The Role of Vitamin D in Inflammatory Bowel Disease - Assessing Therapeutic and Preventive Potential of Supplementation and Food Fortification. Food Technol Biotechnol 2018;56(4):455‑63.
  7. Parizadeh SM, Jafarzadeh-Esfehani R, Hassanian SM, Mottaghi-Moghaddam A, Ghazaghi A, Ghandehari M, et al. Vitamin D in inflammatory bowel disease: From biology to clinical implications. Complement Ther Med 2019;47:102189.
  8. Hagenau T, Vest R, Gissel TN, et al. Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int 2009;20(1):133‑40.
  9. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357(3):266‑81.
  10. Hassannia T, GhaznaviRad E, Vakili R, Taheri S, Rezaee SA. High Prevalence of Vitamin D Deficiency and Associated Risk Factors among Employed Women in a Sunny Industrial City. Int J Vitam Nutr Res 2015;85(3‑4):119‑28.
  11. Trilok Kumar G, Chugh R, Eggersdorfer M. Poor Vitamin D Status in Healthy Populations in India: A Review of Current Evidence. Int J Vitam Nutr Res 2015;85(85):3‑4.
  12. Meddeb N, Sahli H, Chahed M, Abdelmoula J, Feki M, Salah H, et al. Vitamin D deficiency in Tunisia. Osteoporos Int 2005;16(2):180‑3.
  13. Bezrati I, Ben Fradj MK, Ouerghi N, Feki M, Chaouachi A, Kaabachi N. Vitamin D inadequacy is widespread in Tunisian active boys and is related to diet but not to adiposity or insulin resistance. Libyan J Med 2016;11:31258.
  14. Yahyaoui S, Jmal L, Sammoud A, Abdenebi M, Jmal A, Boukthir S. Vitamin D deficiency is associated with metabolic syndrome in Tunisian children with obesity. Tunis Med 2019;97(12):1353‑6.
  15. Fenina H, Chelli D, Ben Fradj MK, Feki M, Sfar E, Kaabachi N. Vitamin D deficiency is widespread in tunisian pregnant women and inversely associated with the level of education. Clin Lab 2016;62(5):801‑6.
  16. Ayadi ID, Nouaili EBH, Talbi E, et al. Prevalence of vitamin D deficiency in mothers and their newborns in a Tunisian population. Int J Gynaecol Obstet 2016;133(2):192‑5.
  17. Azzopardi N, Ellul P. Disease location and severity may predict vitamin D deficiency in Crohn’s. J Crohns Colitis 2014;8(10):1336.
  18. Gilman J, Shanahan F, Cashman KD. Determinants of vitamin D status in adult Crohn’s disease patients, with particular emphasis on supplemental vitamin D use. Eur J Clin Nutr 2006;60(7):889‑96.
  19. Pappa HM, Gordon CM, Saslowsky TM, et al. Vitamin D Status in Children and Young Adults With Inflammatory Bowel Disease. Pediatrics 2006;118(5):1950‑61.
  20. Pappa HM, Langereis EJ, Grand RJ, Gordon CM. Prevalence and risk factors for hypovitaminosis D in young patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2011;53(4):361‑4.
  21. V Valentine JF, Sninsky CA. Prevention and treatment of osteoporosis in patients with inflammatory bowel disease. Am J Gastroenterol 1999;94(4):878‑83.
  22. Tajika M, Matsuura A, Nakamura T, Suzuki T, Sawaki A, Kato T, et al. Risk factors for vitamin D deficiency in patients with Crohn’s disease. J Gastroenterol 2004;39(6):527‑33.
  23. Leichtmann GA, Bengoa JM, Bolt MJ, Sitrin MD. Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with both Crohn’s disease and intestinal resection. Am J Clin Nutr 1991;54(3):548‑52.
  24. Bruyn JR, van Heeckeren R, Ponsioen CY, et al. Vitamin D deficiency in Crohn’s disease and healthy controls: A prospective case-control study in the Netherlands. J Crohns Colitis 2014;8(10):1267‑73.
  25. Belen E, Aykan AC, Kalaycioglu E, Sungur MA, Sungur A, Cetin M. Low-level vitamin D is associated with atrial fibrillation in patients with chronic heart failure. Adv Clin Exp Med 2016;25(1):51‑7.
  26. Hausmann J, Kubesch A, Amiri M, Filmann N, Blumenstein I. Vitamin D deficiency is associated with increased disease activity in patients with inflammatory bowel disease. J Clin Med 2019;8(9):1319.
  27. Ye L, Lin Z, Liu J, Cao Q. Vitamin D Deficiency is associated with endoscopic severity in patients with crohn’s disease. Gastroenterol Res Pract 2017;2017:4869718.
  28. Mojto V, Kolcunova M, Rausova Z, Chrenova J, Dedik L. The nonskeletal effects of vitamin D3 and the threshold limit associated with the risk of health complications. Bratisl Lek Listy 2016;117(3):133‑6.
  29. Suibhne TN, Cox G, Healy M, O’Morain C, O’Sullivan M. Vitamin D deficiency in Crohn’s disease: prevalence, risk factors and supplement use in an outpatient setting. J Crohns Colitis 2012;6(2):182‑8.
  30. Ulitsky A, Ananthakrishnan AN, Naik A, et al. Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life. J Parenter Enteral Nutr 2011;35(3):308‑16.
  31. Nielsen OH, Rejnmark L, Moss AC. Role of Vitamin D in the Natural History of Inflammatory Bowel Disease. J Crohns Colitis 2018;12(6):742‑52.
  32. Nielsen OH, Hansen TI, Gubatan JM, Jensen KB, Rejnmark L. Managing vitamin D deficiency in inflammatory bowel disease. Frontline Gastroenterol 2019;10(4):394‑400.
  33. Boccuzzi L, Infante M, Ricordi C. The potential therapeutic role of vitamin D in inflammatory bowel disease. Eur Rev Med Pharmacol Sci 2023;27(10):4678‑87.