Effects of Vitamin D Supplementation on Serum 25‑Hydroxy Cholecalciferol in Inflammatory Bowel Diseases: A Meta‑Analysis of Randomized Clinical Trials

Reza Ramezani, Parivash Ghorbaninejad, Masoumeh Eslahi, Leila Sheikhi, Fatemeh Abbasi, Mohaddeseh Hasanzadeh, Saba Mohammadpour, Alireza Milajerdi

Abstract


Background: Earlier studies about the influence of vitamin D (Vit D) supplementation on patients with inflammatory bowel disease (IBD) reported inconsistent results. Current comprehensive systematic review and meta‑analysis was conducted to assess the effect of Vit D supplementation on clinical and subclinical factors in patients with IBD. Methods: PubMed, Scopus, and Web of Science databases were searched for relevant randomized controlled trials (RCTs) on the effect of Vit D supplementation in IBD patients, published up to March 2023. Data were analyzed by the random‑effect model. Heterogeneity was assessed by Cochran’s Q test and I‑square (I2 ) statistic. The mean differences (MDs) were calculated as the summary effect size. Results: We included nine related articles, and our findings indicated that vitamin D administration increased serum vitamin D levels compared to placebo (weighted mean difference (WMD): 12.08; 95% confidence interval (95% CI): 9.06, 15.09; I2 = 97.01%; P < 0.001) in IBD patients. However, it had no significant influence on disease activity (standardized mean difference (SMD): 0.27; 95% CI: ‑0.42, 0.95; I2 = 91.7%; P < 0.001) or serum levels of C‑reactive protein (CRP) (WMD: ‑1.42; 95% CI: ‑3.90, 1.06; I2 = 41.9%; P = 0.262). Conclusions: Current meta‑analysis showed a significant effect of Vit D supplementation on increasing serum cholecalciferol. However, no significant effects of Vit D supplementation on the disease activity and serum levels of CRP were seen. Further studies are needed to expand current knowledge in this issue and found a significant increment in serum 25‑hydroxy cholecalciferol concentrations following Vit D supplementation in IBD patients.

Keywords


Cholecalciferol; inflammatory bowel diseases; meta‑analysis; vitamin D

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References


Ballou S, Keefer L. Psychological interventions for irritable bowel syndrome and inflammatory bowel diseases. Clin Transl Gastroenterol 2017;8:e214.

Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 2000;119:15 22.

Kaplan GG, Ng SC. Understanding and preventing the global increase of inflammatory bowel disease. Gastroenterology 2017;152:313 21.e2.

Park J, Cheon JH. Incidence and prevalence of inflammatory bowel disease across Asia. Yonsei Med J 2021;62:99 108.

Ng SC, Kaplan GG, Tang W, Banerjee R, Adigopula B, Underwood FE, et al. Population density and risk of inflammatory bowel disease: A prospective population based study in 13 countries or regions in Asia Pacific. Am J Gastroenterol 2019;114:107 15.

Burisch J, Jess T, Martinato M, Lakatos PL; ECCO EpiCom oboE. The burden of inflammatory bowel disease in Europe. J Crohns Colitis 2013;7:322 37.

Kappelman MD, Rifas Shiman SL, Porter CQ, Ollendorf DA, Sandler RS, Galanko JA, et al. Direct health care costs of Crohn’s disease and ulcerative colitis in US children and adults. Gastroenterology 2008;135:1907 13.

Safarpour AR, Hosseini SV, Mehrabani D. Epidemiology of inflammatory bowel diseases in iran and Asia; a mini review. Iran J Med Sci 2013;38 (2 Suppl):140 9.

Bours PH, Wielders JP, Vermeijden JR, van de Wiel A. Seasonal variation of serum 25 hydroxyvitamin D levels in adult patients with inflammatory bowel disease. Osteoporosis Int 2011;22:2857 67.

Scotti GB, Afferri MT, De Carolis A, Vaiarello V, Fassino V, Ferrone F, et al. Factors affecting vitamin D deficiency in active inflammatory bowel diseases. Dig Liver Dis 2019;51:657 62.

Wilson J, Hair C, Knight R, Catto Smith A, Bell S, Kamm M, et al. High incidence of inflammatory bowel disease in Australia: A prospective population based Australian incidence study. Inflamm Bowel Dis 2010;16:1550 6.

Nerich V, Jantchou P, Boutron Ruault MC, Monnet E, Weill A, Vanbockstael V, et al. Low exposure to sunlight is a risk factor for Crohn’s disease. Aliment Pharmacol Ther 2011;33:940 5.

Cosnes J, Gower Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 2011;140:1785 94.

Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll like receptor triggering of a vitamin D mediated human antimicrobial response. Science 2006;311:1770 3.

Hewison M. Vitamin D and immune function: An overview. Proc Nutr Soc 2012;71:50 61.

Li J, Chen N, Wang D, Zhang J, Gong X. Efficacy of vitamin D in treatment of inflammatory bowel disease: A meta analysis. Medicine 2018;97:e12662.

Guzman Prado Y, Samson O, Segal JP, Limdi JK, Hayee B. Vitamin D Therapy in adults with inflammatory bowel disease: A systematic review and meta analysis. Inflamm Bowel Dis 2020;26:1819 30.

Fletcher J, Cooper SC, Ghosh S, Hewison M. The role of vitamin D in inflammatory bowel disease: Mechanism to management. Nutrients 2019;11:1019.

Vernia F, Valvano M, Longo S, Cesaro N, Viscido A, Latella G. Vitamin D in inflammatory bowel diseases. Mechanisms of action and therapeutic implications. Nutrients 2022;14:269.

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta analyses: The PRISMA statement. Ann Intern Med 2009;151:264 9, W64.

Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.

Jørgensen SP, Agnholt J, Glerup H, Lyhne S, Villadsen GE, Hvas CL, et al. Clinical trial: Vitamin D3 treatment in Crohn’s disease a randomized double blind placebo controlled study. Aliment Pharmacol Ther 2010;32:377 83.

Bendix M, Dige A, Deleuran B, Dahlerup JF, Jørgensen SP, Bartels LE, et al. Flow cytometry detection of vitamin D receptor changes during vitamin D treatment in Crohn’s disease. Clin Exp Immunol 2015;181:19 28.

Emami MR, Sharifi A, Yaseri M, Derakhshanian H, Hosseinzadeh Attar MJ. Vitamin D suppresses proangiogenic factors in patients with ulcerative colitis: A randomized double blind placebo controlled clinical trial. Complement Ther Clin Pract 2020;39:101086.

Dadaei T, Safapoor MH, Asadzadeh Aghdaei H, Balaii H, Pourhoseingholi MA, Naderi N, et al. Effect of vitamin D3 supplementation on TNF α serum level and disease activity index in Iranian IBD patients. Gastroenterol Hepatol Bed Bench 2015;8:49 55.

Sharifi A, Hosseinzadeh Attar MJ, Vahedi H, Nedjat S. A randomized controlled trial on the effect of vitamin D3 on inflammation and cathelicidin gene expression in ulcerative colitis patients. Saudi J Gastroenterol 2016;22:316 23.

Arihiro S, Nakashima A, Matsuoka M, Suto S, Uchiyama K, Kato T, et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza and upper respiratory infection in patients with inflammatory bowel disease. Inflamm Bowel Dis 2019;25:1088 95.

Tan B, Li P, Lv H, Yang H, Li Y, Li J, et al. Treatment of vitamin D deficiency in Chinese inflammatory bowel disease patients: A prospective, randomized, open label, pilot study. J Dig Dis 2018;19:215 24.

Raftery T, Martineau AR, Greiller CL, Ghosh S, McNamara D, Bennett K, et al. Effects of vitamin D supplementation on intestinal permeability, cathelicidin and disease markers in Crohn’s disease: Results from a randomised double blind placebo controlled study. United European Gastroenterol J 2015;3:294 302.

de Bruyn JR, Bossuyt P, Ferrante M, West RL, Dijkstra G, Witteman BJ, et al. High dose vitamin D does not prevent postoperative recurrence of Crohn’s disease in a randomized placebo controlled trial. Clin Gastroenterol Hepatol 2021;19:1573 82.e5.

Hassan V, Hassan S, Seyed Javad P, Ahmad K, Asieh H, Maryam S, et al. Association between Serum 25 (OH) vitamin D concentrations and inflammatory bowel diseases (IBDs) activity. Med J Malaysia 2013;68:34 8.

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.

Miheller P, Muzes G, Hritz I, Lakatos G, Pregun I, Lakatos PL, et al. Comparison of the effects of 1,25 dihydroxyvitamin D and 25 hydroxyvitamin D on bone pathology and disease activity in Crohn’s disease patients. Inflamm Bowel Dis 2009;15:1656 62.

Tabatabaeizadeh SA, Tafazoli N, Ferns GA, Avan A, Ghayour Mobarhan M. Vitamin D, the gut microbiome and inflammatory bowel disease. J Res Med Sci 2018;23:75.

Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up regulated in myeloid cells by 1,25 dihydroxyvitamin D3. FASEB J 2005;19:1067 77.

Wang TT, Dabbas B, Laperriere D, Bitton AJ, Soualhine H, Tavera Mendoza LE, 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 31.

Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: Vitamins A and D take centre stage. Nat Rev Immunol 2008;8:685 98.

Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, et al. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase 1. J Immunol 2012;188:2127 35.

Zhao H, Zhang H, Wu H, Li H, Liu L, Guo J, et al. Protective role of 1,25(OH) 2 vitamin D3 in the mucosal injury and epithelial barrier disruption in DSS induced acute colitis in mice. BMC Gastroenterol 2012;12:57.

Mokhtari Z, Hosseini E, Zaroudi M, Gibson DL, Hekmatdoost A, Mansourian M, et al. The effect of vitamin D supplementation on serum 25 hydroxy vitamin D in the patients undergoing bariatric surgery: A systematic review and meta analysis of randomized clinical trials. Obes Surg 2022;32:3088 103.