Abstract
Background
Vitamin D, as potential immune modulator, has been implicated as an environmental risk factor for Crohn’s disease (CD). Vitamin D status may be associated with disease risk, severity, activity, and progression. While associations between circulating 25OHD and markers of disease activity and inflammation in CD have been reported, the results are inconsistent.
Aim
To determine the association between vitamin D status and markers of disease activity and inflammation in CD.
Methods
One hundred and nineteen CD patients’ active and inactive diseases were enrolled in the cross-sectional study. Subject demographics and clinical data were collected. A serum sample was collected for 25OHD and CRP analysis, and a stool sample was collected for fecal calprotectin (FC) measurement.
Results
The mean serum 25OHD concentration of the group was 59.8 (24.9) nmol/L. After controlling for confounding variables, serum 25OHD inversely correlated with FC (r = −0.207, P = 0.030), particularly among those in clinical remission (r = −0.242, P = 0.022). The association between FC and 25OHD was further confirmed by linear regression (r = 31.3 %, P < 0.001). FC was lower in patients with 25OHD levels ≥75 nmol/L compared with levels <25 nmol/L [FC: 32.2 (16.3–98.2) vs 100.0 (34.4–213.5) μg/g, P = 0.004]. In the current study, however, 25OHD was not significantly associated with either CRP or CDAI.
Conclusion
Circulating 25OHD was significantly inversely associated with intestinal inflammation as determined by FC in CD. Subgroup analysis confirmed the association among those in clinical remission, but not in those with active disease. 25OHD was not associated with disease activity score (CDAI) or systemic inflammation (CRP). Vitamin D intervention studies are warranted to determine whether raising serum 25OHD levels in patients with CD may reduce intestinal inflammation as measured by FC.
Similar content being viewed by others
References
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;6:182–188.
Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2011;60:571–607.
Bernstein CN, Leslie WD, Leboff MS. AGA technical review on osteoporosis in gastrointestinal diseases. Gastroenterology. 2003;124:795–841.
Jørgensen SP, Agnholt J, Glerup H, et al. Clinical trial: vitamin D3 treatment in Crohn’s disease—a randomized double-blind placebo-controlled study. Aliment Pharmacol Ther. 2010;32:377–383.
Ham M, Longhi MS, Lahiff C, Cheifetz A, Robson S, Moss AC. Vitamin d levels in adults with Crohn’s disease are responsive to disease activity and treatment. Inflamm Bowel Dis. 2014;20:856–860.
Ananthakrishnan AN, Khalili H, Higuchi LM, et al. Higher predicted vitamin D status is associated with reduced risk of Crohn’s disease. Gastroenterology. 2012;142:482–489.
Garg M, Rosella O, Lubel JS, Gibson PR. Association of circulating vitamin D concentrations with intestinal but not systemic inflammation in inflammatory bowel disease. Inflamm Bowel Dis. 2013;19:2634–2643.
Jørgensen SP, Hvas CL, Agnholt J, Christensen LA, Heickendorff L, Dahlerup JF. Active Crohn’s disease is associated with low vitamin D levels. J Crohns Colitis. 2013;7:e407–e413.
Schoepfer AM, Beglinger C, Straumann A, et al. Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn’s disease (SES-CD) than CRP, blood leukocytes, and the CDAI. Am J Gastroenterol. 2010;105:162–169.
Pedersen N, Thielsen P, Martinsen L, et al. eHealth: individualization of mesalazine treatment through a self-managed Web-based solution in mild-to-moderate ulcerative colitis. Inflamm Bowel Dis. 2014;20:2276–2285.
Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1995;854:1–452.
Silverberg MS, Satsangi J, Ahmad T, et al. 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. 2005;19 Suppl A:5A–36A.
Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–1930.
Laird E, McNulty H, Ward M, et al. Vitamin D deficiency is associated with inflammation in older Irish adults. J Clin Endocrinol Metab. 2014;99:1807–1815.
Best WR, Becktel JM, Singleton JW, Kern F. Development of a Crohn’s disease activity index. National Cooperative Crohn’s Disease Study. Gastroenterology. 1976;70:439–444.
Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132:52–65.
D’Haens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis. 2012;18:2218–2224.
Ananthakrishnan AN, Cheng SC, Cai T, et al. Association between reduced plasma 25-hydroxy vitamin D and increased risk of cancer in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2014;12:821–827.
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. JPEN J Parenter Enteral Nutr. 2011;35:308–316.
Joseph AJ, George B, Pulimood AB, Seshadri MS, Chacko A. 25 (OH) vitamin D level in Crohn’s disease: association with sun exposure & disease activity. Indian J Med Res. 2009;130:133–137.
Kelly P, Suibhne TN, O’Morain C, O’Sullivan M. Vitamin D status and cytokine levels in patients with Crohn’s disease. Int J Vitam Nutr Res. 2011;81:205–210.
Elliott PR, Lennard-Jones JE, Hathway N. Simple index of Crohn’s disease activity. Lancet. 1980;1:876.
Sipponen T, Kärkkäinen P, Savilahti E, et al. Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn’s disease and histological findings. Aliment Pharmacol Ther. 2008;28:1221–1229.
Sipponen T, Savilahti E, Kolho KL, Nuutinen H, Turunen U, Färkkilä M. Crohn’s disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn’s disease activity index and endoscopic findings. Inflamm Bowel Dis. 2008;14:40–46.
Yang L, Weaver V, Smith JP, Bingaman S, Hartman TJ, Cantorna MT. Therapeutic effect of vitamin d supplementation in a pilot study of Crohn’s patients. Clin Transl Gastroenterol. 2013;4:e33.
Raftery T, Martineau A, Greiller C, et al. Does vitamin D supplementation impact plasma cathelicidin, human beta defensin 2 and intestinal permeability in stable Crohn’s disease? Results from a randomised, double blind placebo controlled study. Proc Nutr Soc. 2013;72:E176.
Cannell JJ, Hollis BW. Use of vitamin D in clinical practice. Altern Med Rev. 2008;13:6–20.
Røseth AG, Aadland E, Grzyb K. Normalization of faecal calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease. Scand J Gastroenterol. 2004;39:1017–1020.
Molander P, af Björkesten CG, Mustonen H, et al. Fecal calprotectin concentration predicts outcome in inflammatory bowel disease after induction therapy with TNFα blocking agents. Inflamm Bowel Dis. 2012;18:2011–2017.
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;60:889–896.
de 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;8:1267–1273.
Driscoll RH, Meredith SC, Sitrin M, Rosenberg IH. Vitamin D deficiency and bone disease in patients with Crohn’s disease. Gastroenterology. 1982;83:1252–1258.
Hollander D, Truscott TC. Mechanism and site of small intestinal uptake of vitamin D3 in pharmacological concentrations. Am J Clin Nutr. 1976;29:970–975.
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;54:548–552.
Emmen JM, Wielders JP, Boer AK, van den Ouweland JM, Vader HL. The new Roche vitamin D total assay: fit for its purpose? Clin Chem Lab Med. 2012;50:1969–1972.
Cantorna MT, Munsick C, Bemiss C, Mahon BD. 1,25-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr. 2000;130:2648–2652.
Froicu M, Cantorna MT. Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury. BMC Immunol. 2007;8:5.
Acknowledgments
TR is supported by the Irish Research Council (IRC) and Sarah Purser Medical Research Award from Trinity College, Dublin. These organizations had no involvement in the study other than grant funding. The authors acknowledge and thank the study participants.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Raftery, T., Merrick, M., Healy, M. et al. Vitamin D Status Is Associated with Intestinal Inflammation as Measured by Fecal Calprotectin in Crohn’s Disease in Clinical Remission. Dig Dis Sci 60, 2427–2435 (2015). https://doi.org/10.1007/s10620-015-3620-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-015-3620-1