Levels of Vitamin D Are Low After Crohn's Disease Is Established But Not Before

Berkeley N. Limketkai, Manish B. Singla, Benjamin Rodriguez, Ganesh R. Veerappan, John D. Betteridge, Miguel A. Ramos, Susan M. Hutfless, Steven R. Brant

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background & Aims: Low serum levels of vitamin D have been associated with Crohn's disease (CD). However, it is unclear whether low vitamin D levels cause CD or CD reduces serum vitamin D. Methods: United States military personnel with CD (n = 240) and randomly selected individuals without CD (controls, n = 240) were matched by age, sex, race, military branch, and geography. We measured 25-hydroxyvitamin D in sera 8–3 years (pre-2) and 3 years to 3 months before diagnosis (pre-1) and 3 months before through 21 months after diagnosis (pre-0). We genotyped VDR and GC vitamin D related polymorphisms. We used conditional logistic regression, including adjustments for smoking, season, enlistment status, and deployment, to estimate relative odds of CD according to vitamin D levels and interactions between genetic factors and levels of vitamin D. Results: Levels of vitamin D before diagnosis were not associated with CD in pre-2 (P trend = .65) or pre-1 samples (P trend = .84). However, we found an inverse correlation between CD and highest tertile of vitamin D level in post-diagnosis samples (P trend = .01; odds ratio, 0.51; 95% CI, 0.30–0.86). Interactions were not detected between vitamin D levels and VDR or GC polymorphisms. We observed an association between VDR Taq1 polymorphism and CD (independent of vitamin D) (P = .02). Conclusions: In serum samples from military personnel with CD and matched controls, we found no evidence for an association between CD and vitamin D levels up to 8 years before diagnosis. However, we observed an inverse-association between post-diagnosis vitamin D levels and CD. These findings suggest that low vitamin D does not contribute to development of CD—instead, CD leads to low vitamin D.

Original languageEnglish (US)
Pages (from-to)1769-1776.e1
JournalClinical Gastroenterology and Hepatology
Issue number8
StatePublished - Jul 2020
Externally publishedYes


  • Autoimmune
  • Epidemiology
  • Etiology
  • Genetics
  • IBD
  • Inflammatory Bowel Disease
  • Nutrition
  • Reverse Causation

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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