Effect of vitamin D on Helicobacter pylori infection and eradication: An updated systematic review and meta-analysis

Document Type : Review


1 Department of Community Medicine and Behavioural Sciences, Faculty of Medicine, Kuwait University, Kuwait

2 Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran

3 Besat Hospital, Kurdistan University of Medical Sciences, Sanandaj, Iran

4 Social Determinants of Health Research, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran


Background: Various studies that have examined the association between Helicobacter pylori (H pylori) and vitamin D (25-hydroxyvitamin D [25(OH)D]) have reported different and sometimes controversial results.
Objectives: This systematic review and meta-analysis was performed to investigate the relationship between vitamin D and H. pylori infection and its eradication.
Methods: Observational studies published in English were searched in PubMed, Scopus, and ISI databases up to August 1, 2021. The odds ratio of H. pylori infection and eradication in the low vitamin D group and the control group was calculated using the standardized mean difference (SMD). The pooled estimate was calculated using a random effects model. Heterogeneity was assessed using Cochran's Q test and the I2 index.
Results: Twelve studies were analyzed in this meta-analysis, and the results showed that the level of 25(OH)D in H pylori‐positive patients was significantly lower than those without infection (SMD = -0.66 ng/mL, 95% CI: -0.99, -0.33, P<0.001). Also, the level of 25(OH)D in H. pylori successful eradication individuals was significantly higher than those with unsuccessful eradication (SMD = 1.53 ng/mL, 95% CI: 1.34–1.71, P<0.001).
Conclusion: There is a significant relationship between vitamin D levels and H. pylori infection and its eradication. Therefore, paying attention to vitamin D levels when treating H. pylori infection is necessary.


Main Subjects

  1. Sokwala A, Shah MV, Devani S, Yonga G. Helicobacter pylori eradication: A randomised comparative trial of 7-day versus 14-day triple therapy. S Afr Med J. 2012;102(6). doi:10.7196/SAMJ.5302 PMid:22668909
  2. Rana R, Wang SL, Li J, Wang Y, Rao Q, Yang C. Helicobacter pylori infection: A recent approach to diagnosis and management. J Biomed. 2017; 2(1):45-56. doi:10.7150/jbm.17612
  3. Surmeli DM, Surmeli ZG, Bahsi R, Turgut T, Oztorun HS, Atmis V, et al. Vitamin D deficiency and risk of Helicobacter pylori infection in older adults: a cross-sectional study. Aging Clin Exp Res. 2019;31(7):985-91. doi:10.1007/s40520-018-1039-1 PMid:30267333
  4. Graham DY, Malaty HM, Evans DG, Evans Jr DJ, Klein PD, Adam E. Epidemiology of Helicobacter pylori in an asymptomatic population in the United States: effect of age, race, and socioeconomic status. Gastroenterology. 1991;100(6): 1495-501. doi:10.1016/0016-5085(91)90644-Z PMid:2019355
  5. Khalifa MM, Sharaf RR, Aziz RK. Helicobacter pylori: a poor man's gut pathogen? Gut Pathog. 2010;2(1):1-12. doi:10.1186/1757-4749-2-2 PMid:20356368 PMCid:PMC2861632
  6. Brown LM. Helicobacter pylori: epidemiology and routes of transmission. Epidemiol Rev. 2000;22(2):283-97. doi:10.1093/oxfordjournals.epirev.a018040PMid:11218379
  7. Hunt R, Xiao S, Megraud F, Leon-Barua R, Bazzoli F, Van der Merwe S, et al. Helicobacter pylori in developing countries. World gastroenterology organisation global guideline. J Gastrointestin Liver Dis. 2011;20(3):299-304.
  8. Goh KL, Chan WK, Shiota S, Yamaoka Y. Epidemiology of Helicobacter pylori infection and public health implications. Helicobacter. 2011;16:1-9. doi:10.1111/j.1523-5378.2011.00874.x PMid:21896079 PMCid:PMC3719046
  9. DuBois S, Kearney DJ. Iron-deficiency anemia and Helicobacter pylori infection: a review of the evidence. Clin Transl Gastroenterol. 2005;100(2):453-9. doi:10.1111/j.1572-0241.2005.30252.x PMid:15667507
  10. Haider AW, Wilson PW, Larson MG, Evans JC, Michelson EL, Wolf PA, et al. The association of seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease: a prospective study. J Am Coll Cardiol. 2002;40(8):1408-13. doi:10.1016/S0735-1097(02)02272-6 PMid:12392829
  11. Kountouras J, Boziki M, Gavalas E, Zavos C, Grigoriadis N, Deretzi G, et al. Eradication of Helicobacter pylori may be beneficial in the management of Alzheimer's disease. J Neurol. 2009;256(5):758-67. doi:10.1007/s00415-009-5011-z PMid:19240960
  12. Kountouras J, Tsolaki M, Gavalas E, Boziki M, Zavos C, Karatzoglou P, et al. Relationship between Helicobacter pylori infection and Alzheimer disease. Neurology. 2006;66(6):938-40. doi:10.1212/01.wnl.0000203644.68059.5f PMid:16567719
  13. Rathbone B, Martin D, Stephens J, Thompson JR, Samani NJ. Helicobacter pylori seropositivity in subjects with acute myocardial infarction. Heart. 1996;76(4):308-11. doi:10.1136/hrt.76.4.308 PMid:8983674 PMCid:PMC484539
  14. NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus development panel on Helicobacter pylori in peptic ulcer disease. JAMA. 1994;272:65-9. doi:10.1001/jama.272.1.65 PMid:8007082
  15. Chey WD, Wong BC, Gastroenterology PPCotACo, ACG. American College of Gastroenterology guideline on the management of Helicobacter pylori infection.  J Am Coll Gastroenterol. 2007;102(8):1808-25. doi:10.1111/j.1572-0241.2007.01393.x PMid:17608775
  16. Lu C, Yu Y, Li L, Yu C, Xu P. Systematic review of the relationship of Helicobacter pylori infection with geographical latitude, average annual temperature and average daily sunshine. BMC Gastroenterol. 2018; 18 (1):1-9. doi:10.1186/s12876-018-0779-x PMid:29665777 PMCid:PMC5905136
  17. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-81. doi:10.1056/NEJMra070553 PMid:17634462
  18. Sullivan SS, Rosen CJ, Halteman WA, Chen TC, Holick MF. Adolescent girls in Maine are at risk for vitamin D insufficiency. J Am Diet Assoc. 2005;105(6):971-4. doi:10.1016/j.jada.2005.03.002 PMid:15942551
  19. Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, et al. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology. 2012;79 (13): 1397-405. doi:10.1212/WNL.0b013e31826c197f PMid:23008220 PMCid:PMC3448747
  20. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck A, Theiler R, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. 2009;339. doi:10.1136/bmj.b3692 PMid:19797342 PMCid:PMC2755728
  21. Bischoff-Ferrari HA, Dietrich T, Orav EJ, Hu FB, Zhang Y, Karlson EW, et al. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged≥ 60 y. Am J Clin Nutr. 2004;80(3):752-8. doi:10.1093/ajcn/80.3.752 PMid:15321818
  22. Jenab M, Bueno-de-Mesquita HB, Ferrari P, van Duijnhoven FJ, Norat T, Pischon T, et al. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case-control study. BMJ. 2010; 340.
  23. Lee DM, Tajar A, O'Neill TW, O'Connor DB, Bartfai G, Boonen S, et al. Lower vitamin D levels are associated with depression among community-dwelling European men. J Psychopharmacol. 2011; 25(10):1320-8. doi:10.1177/0269881110379287 PMid:20823081
  24. Wang L, Song Y, Manson JE, Pilz S, März W, Michaëlsson K, et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes. 2012;5(6):819-29. doi:10.1161/CIRCOUTCOMES.112.967604 PMid:23149428 PMCid:PMC3510675          
  25. Basyigit S, Unsal O, Uzman M, Sapmaz F, Dogan OC, Kefeli A, et al. Relationship between Helicobacter pylori infection and celiac disease: a cross-sectional study and a brief review of the literature. Prz Gastroenterol. 2017;12(1):49. doi:10.5114/pg.2017.65681 PMid:28337237 PMCid:PMC5360666
  26. Kawaura A, Takeda E, Tanida N, Nakagawa K, Yamamoto H, Sawada K, et al. Inhibitory effect of long term 1α-hydroxyvitamin D3 administration on Helicobacter pylori infection. J Clin Biochem Nutr. 2006; 38(2):103-6. doi:10.3164/jcbn.38.103
  27. Antico A, Tozzoli R, Giavarina D, Tonutti E, Bizzaro N. Hypovitaminosis D as predisposing factor for atrophic type A gastritis: a case-control study and review of the literature on the interaction of vitamin D with the immune system. Clin Rev Allergy Immunol. 2012;42(3):355-64. doi:10.1007/s12016-011-8255-1 PMid:21286859
  28. Assaad S, Chaaban R, Tannous F, Costanian C. Dietary habits and Helicobacter pylori infection: a cross sectional study at a Lebanese hospital. BMC Gastroenterol. 2018;18(1):1-13. doi:10.1186/s12876-018-0775-1 PMid:29661143 PMCid:PMC5902873
  29. El Shahawy MS, Hemida MH, El Metwaly I, Shady ZM. The effect of vitamin D deficiency on eradication rates of Helicobacter pylori infection. JGH Open. 2018;2(6):270-5. doi:10.1002/jgh3.12081 PMid:30619936 PMCid:PMC6308038
  30. Gerig R, Ernst B, Wilms B, Thurnheer M, Schultes B. Preoperative nutritional deficiencies in severely obese bariatric candidates are not linked to gastric Helicobacter pylori infection. Obes Surg. 2013;23(5):698-702. doi:10.1007/s11695-013-0878-2 PMid:23430478
  31. Han C, Ni Z, Yuan T, Zhang J, Wang C, Wang X, et al. Influence of serum vitamin D level on Helicobacter pylori eradication: A multi‐center, observational, prospective and cohort study. J Dig Dis. 2019;20(8):421-6. doi:10.1111/1751-2980.12793 PMid:31145549 PMCid:PMC6851741
  32. Huang B YS, Chen C, Ye S. Effect of 25-hydroxyvitamin D on Helicobacter pylori eradication in patients with type 2 diabetes. Wien Klin Wochenschr Educ. 2019;131(3):75-80. doi:10.1007/s00508-018-1416-y PMid:30542778 PMCid:PMC6394653
  33. Ibrahim HA. Relationship Between Helicobacter pylori Infection, Serum Vitamin D3 Level and Spontaneous Abortion. Int J Gen Med. 2020;13:469. doi:10.2147/IJGM.S251075 PMid:32801841 PMCid:PMC7395681
  34. Korkmaz H, IPEKCI S, Baldane S, Sozen M, Abusoglu S, Kebapcilar L. Examining the relationship between vitamin D levels and Helicobacter pylori infection and its effect on the hypothalamic-pituitary-adrenal axis in dyspeptic patients. J Exp Clin Med. 2015;32(3).
  35. Magsi I. Response of Helicobacter Pylori Eradication Treatment in Patients With Normal and Below-Normal Serum Vitamin D Levels. Cureus. 2021;13(4). doi:10.7759/cureus.14777
  36. Shatla MM, Faisal AS, El-Readi MZ. Is Vitamin D Deficiency a Risk Factor for Helicobacter Pylori Eradication Failure? Clin Lab. 2021;67(2). doi:10.7754/Clin.Lab.2020.200118 PMid:33616339
  37. Yildirim O, Yildirim T, Seckin Y, Osanmaz P, Bilgic Y, Mete R. The influence of vitamin D deficiency on eradication rates of Helicobacter pylori. Adv Clin Exp Med. 2017;26(9):1377-81. doi:10.17219/acem/65430 PMid:29442458
  38. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097 PMid:19621072 PMCid:PMC2707599
  39. Lo CK-L, Mertz D, Loeb M. Newcastle-Ottawa Scale: comparing reviewers' to authors' assessments. BMC Med Res Methodol. 2014; 14(1):1-5. doi:10.1186/1471-2288-14-45 PMid:24690082 PMCid:PMC4021422
  40. Higgins J, Altman D. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0. 0 (updated February 2008). The Cochrane Collaboration, 2008. Available from www.cochrane‐handbook.org. 2008. doi:10.1002/9780470712184
  41. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557-60. doi:10.1136/bmj.327.7414.557 PMid:12958120 PMCid:PMC192859
  42. Patsopoulos NA, Evangelou E, Ioannidis JP. Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol. 2008;37(5):1148-57. doi:10.1093/ije/dyn065 PMid:18424475 PMCid:PMC6281381
  43. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315 (7109):629-34. doi:10.1136/bmj.315.7109.629 PMid:9310563 PMCid:PMC2127453
  44. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994:1088-101. doi:10.2307/2533446 PMid:7786990
  45. Hong J, Kim S, Chung K, Kim E, Jung J, Park M, et al. Association between vitamin D deficiency and tuberculosis in a Korean population. Int J Tuberc Lung Dis. 2014;18(1):73-8. doi:10.5588/ijtld.13.0536 PMid:24365556
  46. Hosoda K, Shimomura H, Wanibuchi K, Masui H, Amgalanbaatar A, Hayashi S, et al. Identification and characterization of a vitamin D 3 decomposition product bactericidal against Helicobacter pylori. Sci Rep. 2015; 5(1):1-9. doi:10.1038/srep08860 PMid:25749128 PMCid:PMC4352922
  47. Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut Pathog. 2007; 56 (6):772-81. doi:10.1136/gut.2006.101634 PMid:17170018 PMCid:PMC1954853
  48. Lu C, Yang J, Yu W, Li D, Xiang Z, Lin Y, et al. Association between 25 (OH) D level, ultraviolet exposure, geographical location, and inflammatory bowel disease activity: a systematic review and meta-analysis. PloS one. 2015;10(7):e0132036. doi:10.1371/journal.pone.0132036 PMid:26172950 PMCid:PMC4501705
  49. Yang L, He X, Li L, Lu C. Effect of vitamin D on Helicobacter pylori infection and eradication: A meta‐analysis. Helicobacter. 2019;24(5):e12655. doi:10.1111/hel.12655 PMCid:PMC6790945
  50. Guo L, Chen W, Zhu H, Chen Y, Wan X, Yang N, et al. Helicobacter pylori Induces Increased Expression of the Vitamin D Receptor in Immune Responses. Helicobacter. 2014;19(1):37-47. doi:10.1111/hel.12102 PMid:24188043