Skip to main content
Top
Published in: Digestive Diseases and Sciences 2/2021

01-02-2021 | Ulcerative Colitis | Original Article

Influence of Severe Vitamin D Deficiency on the Clinical Course of Inflammatory Bowel Disease

Authors: Nam Seok Ham, Sung Wook Hwang, Eun Hye Oh, Jeongseok Kim, Ho-Su Lee, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang

Published in: Digestive Diseases and Sciences | Issue 2/2021

Login to get access

Abstract

Background

Previous studies have shown vitamin D status to be associated with disease activity in patients with inflammatory bowel disease (IBD), but its influence on the clinical course of IBD has not been established.

Aims

We aimed to analyze whether the serum 25-hydroxyvitamin D3 [25(OH)D] status is associated with clinical characteristics and affects the risk of surgery in patients with IBD.

Methods

From the IBD registry of the Asan Medical Center, we identified all patients who had at least one 25(OH)D measurement; we then analyzed the association between clinical factors and 25(OH)D status. 25(OH)D was considered borderline deficient, deficient, and severely deficient at levels of < 30, < 20, and < 10 ng/mL, respectively.

Results

We included 711 Crohn’s disease (CD) and 764 ulcerative colitis (UC) patients who had not undergone surgery before 25(OH)D was measured. Both in CD and in UC patients, reduced 25(OH)D was associated with higher disease activity scores and CRP levels (p < 0.001). Severe 25(OH)D deficiency was associated with ileocolonic disease and complicated behavior in CD (p < 0.05) and was relevant to the disease extent in UC (p < 0.001). Additionally, severe 25(OH)D deficiency was associated with CMV colitis in patients with UC (p < 0.001). In multivariable analysis, severe deficiency of 25(OH)D was an independent risk factor for surgery in both CD (HR 1.93, 95% confidence interval [CI] 1.38–2.70) and UC (HR 2.77, 95% CI 1.14–6.74).

Conclusion

Severe 25(OH)D deficiency may be a marker of a more aggressive clinical course of IBD.
Literature
1.
go back to reference Park SH, Kim YJ, Rhee KH, et al. A 30-year trend analysis in the epidemiology of inflammatory bowel disease in the Songpa-Kangdong District of Seoul, Korea in 1986–2015. J Crohn’s Colitis. 2019;13:1410–1417.CrossRef Park SH, Kim YJ, Rhee KH, et al. A 30-year trend analysis in the epidemiology of inflammatory bowel disease in the Songpa-Kangdong District of Seoul, Korea in 1986–2015. J Crohn’s Colitis. 2019;13:1410–1417.CrossRef
2.
go back to reference Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet. 2017;389:1756–1770.CrossRef Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet. 2017;389:1756–1770.CrossRef
3.
go back to reference Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn’s disease. Lancet. 2017;389:1741–1755.CrossRef Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn’s disease. Lancet. 2017;389:1741–1755.CrossRef
4.
go back to reference Weisshof R, Chermesh I. Micronutrient deficiencies in inflammatory bowel disease. Curr Opin Clin Nutr Metab Care. 2015;18:576–581.CrossRef Weisshof R, Chermesh I. Micronutrient deficiencies in inflammatory bowel disease. Curr Opin Clin Nutr Metab Care. 2015;18:576–581.CrossRef
5.
go back to reference Hwang C, Ross V, Mahadevan U. Micronutrient deficiencies in inflammatory bowel disease: from A to zinc. Inflamm Bowel Dis. 2012;18:1961–1981.CrossRef Hwang C, Ross V, Mahadevan U. Micronutrient deficiencies in inflammatory bowel disease: from A to zinc. Inflamm Bowel Dis. 2012;18:1961–1981.CrossRef
6.
go back to reference Massironi S, Rossi RE, Cavalcoli FA, Della Valle S, Fraquelli M, Conte D. Nutritional deficiencies in inflammatory bowel disease: therapeutic approaches. Clin Nutr. 2013;32:904–910.CrossRef Massironi S, Rossi RE, Cavalcoli FA, Della Valle S, Fraquelli M, Conte D. Nutritional deficiencies in inflammatory bowel disease: therapeutic approaches. Clin Nutr. 2013;32:904–910.CrossRef
7.
go back to reference 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.CrossRef 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.CrossRef
8.
go back to reference Leslie WD, Miller N, Rogala L, Bernstein CN. Vitamin D status and bone density in recently diagnosed inflammatory bowel disease: the Manitoba IBD Cohort Study. Am J Gastroenterol. 2008;103:1451–1459.CrossRef Leslie WD, Miller N, Rogala L, Bernstein CN. Vitamin D status and bone density in recently diagnosed inflammatory bowel disease: the Manitoba IBD Cohort Study. Am J Gastroenterol. 2008;103:1451–1459.CrossRef
9.
go back to reference Wang TT, Dabbas B, Laperriere D, et al. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem. 2010;285:2227–2231.CrossRef Wang TT, Dabbas B, Laperriere D, et al. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem. 2010;285:2227–2231.CrossRef
11.
go back to reference 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 Enter Nutr. 2011;35:308–316.CrossRef 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 Enter Nutr. 2011;35:308–316.CrossRef
12.
go back to reference Hwang SW. Can vitamin D supplementation help control inflammation in inflammatory bowel disease beyond its classical role in bone health? Intest Res. 2019;17:157–159.CrossRef Hwang SW. Can vitamin D supplementation help control inflammation in inflammatory bowel disease beyond its classical role in bone health? Intest Res. 2019;17:157–159.CrossRef
13.
go back to reference Gomollon F, Dignass A, Annese V, et al. 3rd european evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1—diagnosis and medical management. J Crohn’s Colitis. 2017;11:3–25.CrossRef Gomollon F, Dignass A, Annese V, et al. 3rd european evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1—diagnosis and medical management. J Crohn’s Colitis. 2017;11:3–25.CrossRef
14.
go back to reference Farraye FA, Melmed GY, Lichtenstein GR, Kane SV. Acg clinical guideline: preventive care in inflammatory bowel disease. Am J Gastroenterol. 2017;112:241–258.CrossRef Farraye FA, Melmed GY, Lichtenstein GR, Kane SV. Acg clinical guideline: preventive care in inflammatory bowel disease. Am J Gastroenterol. 2017;112:241–258.CrossRef
15.
go back to reference Magro F, Gionchetti P, Eliakim R, et al. Third european evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohn’s Colitis. 2017;11:649–670.CrossRef Magro F, Gionchetti P, Eliakim R, et al. Third european evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohn’s Colitis. 2017;11:649–670.CrossRef
17.
go back to reference Joseph AJ, George B, Pulimood AB, Seshadri MS, Chacko A. 25 (OH) vitamin D level in Crohn’s disease: association with sun exposure and disease activity. Indian J Med Res. 2009;130:133–137.PubMed Joseph AJ, George B, Pulimood AB, Seshadri MS, Chacko A. 25 (OH) vitamin D level in Crohn’s disease: association with sun exposure and disease activity. Indian J Med Res. 2009;130:133–137.PubMed
18.
go back to reference Nielsen OH, Rejnmark L, Moss AC. Role of vitamin D in the natural history of inflammatory bowel disease. J Crohn’s Colitis. 2018;12:742–752.CrossRef Nielsen OH, Rejnmark L, Moss AC. Role of vitamin D in the natural history of inflammatory bowel disease. J Crohn’s Colitis. 2018;12:742–752.CrossRef
19.
go back to reference Park SH, Yang SK, Park SK, et al. Long-term prognosis of Crohn’s disease and its temporal change between 1981 and 2012: a hospital-based cohort study from Korea. Inflamm Bowel Dis. 2014;20:488–494.CrossRef Park SH, Yang SK, Park SK, et al. Long-term prognosis of Crohn’s disease and its temporal change between 1981 and 2012: a hospital-based cohort study from Korea. Inflamm Bowel Dis. 2014;20:488–494.CrossRef
20.
go back to reference Yang SK, Yun S, Kim JH, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea, 1986–2005: a KASID study. Inflamm Bowel Dis. 2008;14:542–549.CrossRef Yang SK, Yun S, Kim JH, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea, 1986–2005: a KASID study. Inflamm Bowel Dis. 2008;14:542–549.CrossRef
21.
go back to reference Lee HS, Park SH, Yang SK, et al. Long-term prognosis of ulcerative colitis and its temporal change between 1977 and 2013: a hospital-based cohort study from Korea. J Crohn’s Colitis. 2015;9:147–155.CrossRef Lee HS, Park SH, Yang SK, et al. Long-term prognosis of ulcerative colitis and its temporal change between 1977 and 2013: a hospital-based cohort study from Korea. J Crohn’s Colitis. 2015;9:147–155.CrossRef
22.
go back to reference Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–6. discussion 16–19.CrossRef Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–6. discussion 16–19.CrossRef
23.
go back to reference Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55:749–753.CrossRef Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55:749–753.CrossRef
24.
go back to reference 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;19:5A–36A.CrossRef 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;19:5A–36A.CrossRef
25.
go back to reference Park SH, Kim YM, Yang SK, et al. Clinical features and natural history of ulcerative colitis in Korea. Inflamm Bowel Dis. 2007;13:278–283.CrossRef Park SH, Kim YM, Yang SK, et al. Clinical features and natural history of ulcerative colitis in Korea. Inflamm Bowel Dis. 2007;13:278–283.CrossRef
26.
go back to reference Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s disease activity index. National cooperative Crohn’s disease study. Gastroenterology. 1976;70:439–444.CrossRef Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s disease activity index. National cooperative Crohn’s disease study. Gastroenterology. 1976;70:439–444.CrossRef
27.
go back to reference Lewis JD, Chuai S, Nessel L, Lichtenstein GR, Aberra FN, Ellenberg JH. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. 2008;14:1660–1666.CrossRef Lewis JD, Chuai S, Nessel L, Lichtenstein GR, Aberra FN, Ellenberg JH. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. 2008;14:1660–1666.CrossRef
28.
go back to reference Turner D, Seow CH, Greenberg GR, Griffiths AM, Silverberg MS, Steinhart AH. A systematic prospective comparison of noninvasive disease activity indices in ulcerative colitis. Clin Gastroenterol Hepatol. 2009;7:1081–1088.CrossRef Turner D, Seow CH, Greenberg GR, Griffiths AM, Silverberg MS, Steinhart AH. A systematic prospective comparison of noninvasive disease activity indices in ulcerative colitis. Clin Gastroenterol Hepatol. 2009;7:1081–1088.CrossRef
29.
go back to reference Sager K, Alam S, Bond A, Chinnappan L, Probert CS. Review article: cytomegalovirus and inflammatory bowel disease. Aliment Pharmacol Ther. 2015;41:725–733.CrossRef Sager K, Alam S, Bond A, Chinnappan L, Probert CS. Review article: cytomegalovirus and inflammatory bowel disease. Aliment Pharmacol Ther. 2015;41:725–733.CrossRef
30.
go back to reference Bouillon R, Norman AW, Lips P. Vitamin D deficiency. N Engl J Med. 2007;357:1980–1981. author reply 1981–1982.CrossRef Bouillon R, Norman AW, Lips P. Vitamin D deficiency. N Engl J Med. 2007;357:1980–1981. author reply 1981–1982.CrossRef
31.
go back to reference Rosen CJ. Clinical practice. Vitamin D insufficiency. N Engl J Med. 2011;364:248–254.CrossRef Rosen CJ. Clinical practice. Vitamin D insufficiency. N Engl J Med. 2011;364:248–254.CrossRef
32.
go back to reference Need AG, O’Loughlin PD, Morris HA, Coates PS, Horowitz M, Nordin BE. Vitamin D metabolites and calcium absorption in severe vitamin D deficiency. J Bone Miner Res. 2008;23:1859–1863.CrossRef Need AG, O’Loughlin PD, Morris HA, Coates PS, Horowitz M, Nordin BE. Vitamin D metabolites and calcium absorption in severe vitamin D deficiency. J Bone Miner Res. 2008;23:1859–1863.CrossRef
33.
go back to reference Ganji V, Zhang X, Tangpricha V. Serum 25-hydroxyvitamin D concentrations and prevalence estimates of hypovitaminosis D in the U.S. population based on assay-adjusted data. J Nutr. 2012;142:498–507.CrossRef Ganji V, Zhang X, Tangpricha V. Serum 25-hydroxyvitamin D concentrations and prevalence estimates of hypovitaminosis D in the U.S. population based on assay-adjusted data. J Nutr. 2012;142:498–507.CrossRef
34.
go back to reference Choi HS, Oh HJ, Choi H, et al. Vitamin D insufficiency in Korea—a greater threat to younger generation: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008. J Clin Endocrinol Metab. 2011;96:643–651.CrossRef Choi HS, Oh HJ, Choi H, et al. Vitamin D insufficiency in Korea—a greater threat to younger generation: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008. J Clin Endocrinol Metab. 2011;96:643–651.CrossRef
35.
go back to reference Shin YH, Kim KE, Lee C, et al. High prevalence of vitamin D insufficiency or deficiency in young adolescents in Korea. Eur J Pediatr. 2012;171:1475–1480.CrossRef Shin YH, Kim KE, Lee C, et al. High prevalence of vitamin D insufficiency or deficiency in young adolescents in Korea. Eur J Pediatr. 2012;171:1475–1480.CrossRef
36.
go back to reference Han YM, Yoon H, Lim S, et al. Risk factors for vitamin D, zinc, and selenium deficiencies in korean patients with inflammatory bowel disease. Gut Liver. 2017;11:363–369.CrossRef Han YM, Yoon H, Lim S, et al. Risk factors for vitamin D, zinc, and selenium deficiencies in korean patients with inflammatory bowel disease. Gut Liver. 2017;11:363–369.CrossRef
37.
go back to reference Jun JC, Yoon H, Choi YJ, et al. The effect of vitamin D administration on inflammatory markers in patients with inflammatory bowel disease. Intest Res. 2019;17:210–217.CrossRef Jun JC, Yoon H, Choi YJ, et al. The effect of vitamin D administration on inflammatory markers in patients with inflammatory bowel disease. Intest Res. 2019;17:210–217.CrossRef
38.
go back to reference Ananthakrishnan AN, Cagan A, Gainer VS, et al. Normalization of plasma 25-hydroxy vitamin D is associated with reduced risk of surgery in Crohn’s disease. Inflamm Bowel Dis. 2013;19:1921–1927.PubMedPubMedCentral Ananthakrishnan AN, Cagan A, Gainer VS, et al. Normalization of plasma 25-hydroxy vitamin D is associated with reduced risk of surgery in Crohn’s disease. Inflamm Bowel Dis. 2013;19:1921–1927.PubMedPubMedCentral
39.
go back to reference van der Sloot KWJ, Amini M, Peters V, Dijkstra G, Alizadeh BZ. Inflammatory bowel diseases. Inflamm Bowel Dis. 2017;23:1499–1509.CrossRef van der Sloot KWJ, Amini M, Peters V, Dijkstra G, Alizadeh BZ. Inflammatory bowel diseases. Inflamm Bowel Dis. 2017;23:1499–1509.CrossRef
40.
go back to reference Lee HS, Park SH, Kim SH, et al. Risk factors and clinical outcomes associated with cytomegalovirus colitis in patients with acute severe ulcerative colitis. Inflamm Bowel Dis. 2016;22:912–918.CrossRef Lee HS, Park SH, Kim SH, et al. Risk factors and clinical outcomes associated with cytomegalovirus colitis in patients with acute severe ulcerative colitis. Inflamm Bowel Dis. 2016;22:912–918.CrossRef
41.
go back to reference Ananthakrishnan AN, Cagan A, Gainer VS, et al. Higher plasma vitamin D is associated with reduced risk of Clostridium difficile infection in patients with inflammatory bowel diseases. Aliment Pharmacol Ther. 2014;39:1136–1142.CrossRef Ananthakrishnan AN, Cagan A, Gainer VS, et al. Higher plasma vitamin D is associated with reduced risk of Clostridium difficile infection in patients with inflammatory bowel diseases. Aliment Pharmacol Ther. 2014;39:1136–1142.CrossRef
Metadata
Title
Influence of Severe Vitamin D Deficiency on the Clinical Course of Inflammatory Bowel Disease
Authors
Nam Seok Ham
Sung Wook Hwang
Eun Hye Oh
Jeongseok Kim
Ho-Su Lee
Sang Hyoung Park
Dong-Hoon Yang
Byong Duk Ye
Jeong-Sik Byeon
Seung-Jae Myung
Suk-Kyun Yang
Publication date
01-02-2021
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 2/2021
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-020-06207-4

Other articles of this Issue 2/2021

Digestive Diseases and Sciences 2/2021 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine