IBD treated in children by Vitamin D, especially if use more than 2,000 IU daily for 12 weeks – meta-analysis

Created September 2022

Vitamin D therapy in pediatric patients with inflammatory bowel disease: a systematic review and meta-analysis

World J Pediatr. 2022 Sep 13. doi: [10.1007/s12519-022-00605-6]   PDF can be viewed in Deepdyve

Mohammad Hassan Sohouli 1 2 , Fatemeh Farahmand 1 , Hosein Alimadadi 1 , Parisa Rahmani 1 , Farzaneh Motamed 1 , Elma Izze da Silva Magalhães 3 , Pejman Rohani 4 5

Background: There is some evidence for the role of vitamin D deficiency in the pathogenesis of inflammatory bowel disease (IBD) in the pediatric population. However, the results are contradictory. Therefore, we have conducted a systematic review and meta-analysis to evaluated the effect of vitamin D on pediatric patients with IBD.

Methods: We carried out a systematic search in databases from inception until 20 January 2022. We included all relevant articles that evaluate the efficacy and safety of vitamin D on disease activity, inflammatory factors, and vitamin D and calcium levels in pediatric patients with IBD. Random effects models were used to combine the data. The main outcomes were then analyzed using weight mean difference (WMD) and respective 95% confidence interval (CI).

Results: Fifteen treatment arms met the eligibility criteria and were included. Pooled estimates indicated that intervention with vitamin D has a significantly beneficial effect on 25-hydroxyvitamin D3 [25(OH) D3] (pooled WMD of 17.662 ng/mL; CI 9.77-25.46; P < 0.001), calcium (pooled WMD of 0.17 mg/dL; CI 0.04-0.30; P = 0.009), and inflammatory factors including C-reactive protein (CRP) (pooled WMD of -6.57 mg/L; CI -11.47 to -1.67; P = 0.009) and erythrocyte sedimentation rate (ESR) (pooled WMD of -7.94 mm/h; CI -12.65 to -3.22; P = 0.001) levels. In addition, this effect was greater for vitamin D levels at doses greater than 2000 IU, and when follow-up duration was more than 12 weeks.

Conclusion: This study showed that vitamin D therapy can have a significant and beneficial effect on 25(OH) D3, calcium, and inflammatory factors in children and adolescents with IBD.

39 References

  1. Rubalcava NS, Gadepalli SK. Inflammatory bowel disease in children and adolescents. Adv Pediatr. 2021;68:121–42. - DOI

  2. Ye Y, Manne S, Treem WR, Bennett D. Prevalence of inflammatory bowel disease in pediatric and adult populations: recent estimates from large national databases in the United States, 2007–2016. Inflamm Bowel Dis. 2020;26:619–25.

  3. Ananthakrishnan AN, Bernstein CN, Iliopoulos D, Macpherson A, Neurath MF, Ali RAR, et al. Environmental triggers in IBD: a review of progress and evidence. Nat Rev Gastroenterol Hepatol. 2018;15:39–49. - DOI

  4. De Souza HS, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol. 2016;13:13–27. - DOI

  5. Green N, Miller T, Suskind D, Lee D. A review of dietary therapy for IBD and a vision for the future. Nutrients. 2019;11:947. - DOI

  6. Śledzińska K, Landowski P, Żmijewski M, Kamińska B, Kowalski K, Liberek A. Diet, sun, physical activity and vitamin D status in children with inflammatory bowel disease. Nutrients. 2022;14:1029. - DOI

  7. Guzman-Prado Y, Samson O, Segal JP, Limdi JK, Hayee BH. Vitamin D therapy in adults with inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis. 2020;26:1819–30. - DOI

  8. Cantorna MT, Rogers CJ, Arora J. Aligning the paradoxical role of vitamin D in gastrointestinal immunity. Trends Endocrinol Metab. 2019;30:459–66. - DOI

  9. Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390:2769–78. - DOI

  10. Dankers W, Colin EM, Van Hamburg JP, Lubberts E. Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Front Immunol. 2017;7:697. - DOI

  11. Adams JS, Hewison M. Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat Clin Pract Endocrinol Metab. 2008;4:80–90. - DOI

  12. Hradsky O, Soucek O, Maratova K, Matyskova J, Copova I, Zarubova K, et al. Supplementation with 2000 IU of cholecalciferol is associated with improvement of trabecular bone mineral density and muscle power in pediatric patients with IBD. Inflamm Bowel Dis. 2017;23:514–23. - DOI

  13. Jantchou P, Mailhot G, Ezri J, Le Deist F, Deslandres C, Delvin E. P-102: Bioavailability and tolerance of high doses vitamin D in children with newly diagnosed Crohn’s disease. J Crohns Colitis. 2014;8:S432. - DOI

  14. Lee R, Maltz RM, Crandall WV, Plogsted SW, Shaikhkhalil AK, Bowden SA, et al. Single high-dose vitamin D3 supplementation in pediatric patients With inflammatory bowel disease and hypovitaminosis D. J Pediatr Gastroenterol Nutr. 2020;70:e77–80. - DOI

  15. Wingate KE, Jacobson K, Issenman R, Carroll M, Barker C, Israel D, et al. 25-Hydroxyvitamin D concentrations in children with Crohn’s disease supplemented with either 2000 or 400 IU daily for 6 months: a randomized controlled study. J Pediatr. 2014;164:860–5. - DOI

  16. Moran-Lev H, Galai T, Yerushalmy-Feler A, Weisman Y, Anafy A, Deutsch V, et al. Vitamin D decreases hepcidin and inflammatory markers in newly diagnosed inflammatory bowel disease paediatric patients: a prospective study. J Crohns Colitis. 2019;13:1287–91. - DOI

  17. Pappa HM, Mitchell PD, Jiang H, Kassiff S, Filip-Dhima R, DiFabio D, et al. Maintenance of optimal vitamin D status in children and adolescents with inflammatory bowel disease: a randomized clinical trial comparing two regimens. J Clin Endocrinol Metab. 2014;99:3408–17. - DOI

  18. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg. 2021;88:105906. - DOI

  19. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5. - DOI

  20. Higgins J. Cochrane handbook for systematic reviews of interventions. Version 5.1. 0. The Cochrane Collaboration. 2011. https://training.cochrane.org/handbook/current .

  21. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:13. - DOI

  22. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60. - DOI

  23. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34. - DOI

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

  25. Pappa HM, Mitchell PD, Jiang H, Kassiff S, Filip-Dhima R, DiFabio D, et al. Treatment of vitamin D insufficiency in children and adolescents with inflammatory bowel disease: a randomized clinical trial comparing three regimens. J Clin Endocrinol Metab. 2012;97:2134–42. - DOI

  26. Shepherd D, Day AS, Leach ST, Lopez R, Messenger R, Woodhead HJ, et al. Single high-dose oral vitamin D3 therapy (stoss): a solution to vitamin D deficiency in children with inflammatory bowel disease? J Pediatr Gastroenterol Nutr. 2015;61:411–4. - DOI

  27. Benchimol EI, Ward LM, Gallagher J, Rauch F, Barrowman N, Warren J, et al. Effect of calcium and vitamin D supplementation on bone mineral density in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007;45:538–45. - DOI

  28. El Amrousy D, El Ashry H, Hodeib H, Hassan S. Vitamin D in children with inflammatory bowel disease: a randomized controlled clinical trial. J Clin Gastroenterol. 2021;55:815–20.

  29. 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. - DOI

  30. Gubatan J, Chou ND, Nielsen OH, Moss AC. Systematic review with meta-analysis: association of vitamin D status with clinical outcomes in adult patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2019;50:1146–58. - DOI

  31. O’Malley T, Heuberger R. Vitamin D status and supplementation in pediatric gastrointestinal disease. J Spec Pediatr Nurs. 2011;16:140–50. - DOI

  32. Pappa HM, Gordon CM, Saslowsky TM, Zholudev A, Horr B, Shih MC, et al. Vitamin D status in children and young adults with inflammatory bowel disease. Pediatrics. 2006;118:1950–61. - DOI

  33. 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. - DOI

  34. 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 β2 innate immune pathway defective in Crohn disease. J Biol Chem. 2010;285:2227–31. - DOI

  35. 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. - DOI

  36. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O’Garra A. 1α, 25-Dihydroxyvitamin D3 has a direct effect on naive CD4+ T cells to enhance the development of Th2 cells. J Immunol. 2001;167:4974–80. - DOI

  37. 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. - DOI

  38. Zhao H, Zhang H, Wu H, Li H, Liu L, Guo J, et al. Protective role of 1, 25 (OH) 2vitamin D3 in the mucosal injury and epithelial barrier disruption in DSS-induced acute colitis in mice. BMC Gastroenterol. 2012;12:1–14. - DOI

  39. Hlavaty T, Krajcovicova A, Payer J. Vitamin D therapy in inflammatory bowel diseases: who, in what form, and how much? J Crohns Colitis. 2015;9:198–209. - DOI

3+ in infant-Child VitaminDWiki pages with IBD in the title

This list is automatically updated

{LIST()}

51+ VitaminDWiki pages with IBD in the title

This list is automatically updated

{LIST()}

VitaminDWiki - Overview Gut and vitamin D contains

{include}

VitaminDWiki - Overview Gut and vitamin D contains gut-friendly information

{include}

See also VitaminDWiki

50+ related pages have IBS or CROHN'S in their titles

This list is automatically updated

{LIST()}

Tags: Gut Infant-Child Meta-analysis