Gastroenterology

Gastroenterology

Volume 142, Issue 3, March 2012, Pages 482-489
Gastroenterology

Original Research
Clinical—Alimentary Tract
Higher Predicted Vitamin D Status Is Associated With Reduced Risk of Crohn's Disease

https://doi.org/10.1053/j.gastro.2011.11.040Get rights and content

Background & Aims

Vitamin D influences innate immunity, which is believed to be involved in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). However, data examining vitamin D status in relation to risk of CD and UC are lacking.

Methods

We conducted a prospective cohort study of 72,719 women (age, 40–73 y) enrolled in the Nurses’ Health Study. In 1986, women completed an assessment of diet and lifestyle, from which a 25-hydroxy vitamin D [25(OH)D] prediction score was developed and validated against directly measured levels of plasma 25(OH)D. Through 2008, we confirmed reported diagnoses of incident CD or UC through medical record review. We used Cox proportional hazards modeling to examine the hazard ratio (HR) for incident CD or UC after adjusting for potential confounders.

Results

During 1,492,811 person-years of follow-up evaluation, we documented 122 incident cases of CD and 123 cases of UC. The median predicted 25(OH)D level was 22.3 ng/mL in the lowest and 32.2 ng/mL in the highest quartiles. Compared with the lowest quartile, the multivariate-adjusted HR associated with the highest quartile of vitamin D was 0.54 (95% confidence interval [CI], 0.30–.99) for CD (Ptrend = .02) and 0.65 (95% CI, 0.34–1.25) for UC (Ptrend = .17). Compared with women with a predicted 25(OH)D level less than 20 ng/mL, the multivariate-adjusted HR was 0.38 (95% CI, 0.15–0.97) for CD and 0.57 (95% CI, 0.19–1.70) for UC for women with a predicted 25(OH)D level greater than 30 ng/mL. There was a significant inverse association between dietary and supplemental vitamin D and UC, and a nonsignificant reduction in CD risk.

Conclusions

Higher predicted plasma levels of 25(OH)D significantly reduce the risk for incident CD and nonsignificantly reduce the risk for UC in women.

Section snippets

Study Population

The NHS is a prospective cohort that began in 1976 when 121,700 US female registered nurses, ages 30 to 55 years, completed a mailed health questionnaire. With a follow-up response rate of more than 90%, questionnaires have been mailed every 2 years to update health information. In 1980, comprehensive dietary and supplement information was obtained through a validated semiquantitative food frequency questionnaire from which intake of vitamin D could be derived.16, 17 In 1986 the

Results

Among the 72,719 women included, we documented 122 cases of CD and 123 cases of UC during 1,492,811 person-years of follow-up evaluation. At baseline, the median age of participants was 53 years (range, 40–73 y). The median predicted 25(OH)D level was 27.6 ng/mL (range, 7.3–38.6 ng/mL). Table 1 presents the characteristics of the study cohort in 1986 according to the quartile distribution of predicted plasma 25(OH)D level. As expected, women in the lowest quartile of predicted 25(OH)D level had

Discussion

Although deficiency of vitamin D commonly has been described in patients with newly diagnosed IBD,29 it is unclear if this is a consequence of the disease or a contributor to its pathogenesis. In this prospective cohort study, we show that predicted levels of prediagnosis plasma 25(OH)D are associated with a significant reduction in risk of incident CD and nonsignificant reduction in risk of UC over a follow-up period of 22 years. Taken together, our results suggest that vitamin D may be an

Acknowledgments

The authors thank Gideon Aweh for computer programming expertise and acknowledge the dedication of the Nurses Health Study participants and members of Channing Laboratory.

References (49)

  • A. Ascherio et al.

    Correlations of vitamin A and E intakes with the plasma concentrations of carotenoids and tocopherols among American men and women

    J Nutr

    (1992)
  • C. Abraham et al.

    Inflammatory bowel disease

    N Engl J Med

    (2009)
  • R.J. Xavier et al.

    Unravelling the pathogenesis of inflammatory bowel disease

    Nature

    (2007)
  • C.A. Anderson et al.

    Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

    Nat Genet

    (2011)
  • A. Franke et al.

    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

    Nat Genet

    (2010)
  • W.C. Lim et al.

    Mechanisms of disease: vitamin D and inflammatory bowel disease

    Nat Clin Pract Gastroenterol Hepatol

    (2005)
  • K. Martin et al.

    Candidate genes colocalized to linkage regions in inflammatory bowel disease

    Digestion

    (2002)
  • N. Naderi et al.

    Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease

    J Gastroenterol Hepatol

    (2008)
  • J.D. Simmons et al.

    Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility

    Gut

    (2000)
  • R. Dresner-Pollak et al.

    The BsmI vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenazi patients

    Genet Test

    (2004)
  • S. Kimball et al.

    Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis

    J Clin Endocrinol Metab

    (2011)
  • M.F. Holick

    Vitamin D deficiency

    N Engl J Med

    (2007)
  • W.C. Willett et al.

    The use of a self-administered questionnaire to assess diet four years in the past

    Am J Epidemiol

    (1988)
  • E. Giovannucci et al.

    Prospective study of predictors of vitamin D status and cancer incidence and mortality in men

    J Natl Cancer Inst

    (2006)
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    Conflicts of interest These authors disclose the following: Joshua Korzenik has been a consultant for Procter and Gamble, Shire Pharmaceuticals, CytokinePharma, and receives research support from Procter and Gamble and Warner Chilcott; James Richter is a consultant for Policy Analysis, Inc; and Andrew Chan has served as a consultant for Bayer HealthCare and Millennium Pharmaceuticals. The remaining authors disclose no conflicts.

    Funding This work was supported by a Research Scholars Award of the American Gastroenterological Association (A.N.A.), the IBD Working Group (H.K.), the Broad Medical Research Program of the Broad Foundation (A.T.C), and the National Institutes of Health (R01 CA137178, P01 CA87969, P30 DK043351, and K08 DK064256).

    The research presented in this manuscript is original. The contents of this article are solely the responsibility of the authors. The American Gastroenterological Association and the Broad Medical Research Foundation had no role in the collection, management, analysis, or interpretation of the data and had no role in the preparation, review, or approval of the manuscript.

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