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Vitamin B12 deficiency induced by the use of gastric acid inhibitors: Calcium supplements as a potential effect modifier

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The journal of nutrition, health & aging

Abstract

Objective

Use of gastric acid inhibitors has emerged as a risk factor of vitamin B12 deficiency, especially in older adults. Calcium supplements could be an effect modifier of this relationship by its role in the absorption process of vitamin B12. The aim of this study is to examine whether the use of calcium supplements could be an effect modifier of the association between gastric acid inhibitors and vitamin B12 deficiency.

Design

Cross-sectional study based on medical chart reviews.

Setting

Geriatric Assessment Unit (GAU) of a university-affiliated hospital.

Participants

The study included 172 patients discharged from the GAU between 2008 and 2012.

Measurements

Cases of vitamin B12 deficiency were identified as those who had received a diagnosis of vitamin B12 deficiency, and/or were receiving a treatment for vitamin B12 deficiency. Use of gastric acid inhibitors and calcium supplements at admission was determined from the pharmacist report. Associations between medications and vitamin B12 status were investigated using logistic regression models.

Results

Seventy-one patients (41%) had vitamin B12 deficiency. At admission, 42% were taking gastric acid inhibitors and 45% calcium supplements. After adjustment for covariates, analyses revealed that vitamin B12 deficiency was more likely among users of gastric acid inhibitors who did not concomitantly received calcium supplements [OR=3.12; P=0.01]. Conversely, no significant association was observed in patients using both, gastric acid inhibitors and calcium supplements [OR=1.30; P=0.59].

Conclusions

The present study provides the very first evidence that the use of calcium supplements could be an effect modifier of the association between gastric acid inhibitors and vitamin B12 deficiency. Failure to consider calcium supplements as an effect modifier could have led to biased risk estimates in previous published studies.

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References

  1. Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12). Ann Intern Med 1994;120:211–215.

    Article  CAS  PubMed  Google Scholar 

  2. Saltzman JR, Kemp JA, Golner BB, Pedrosa MC, Dallal GE, Russell RM. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. J Am Coll Nutr 1994;13:584–591.

    Article  CAS  PubMed  Google Scholar 

  3. Schenk BE, Festen HP, Kuipers EJ, Klinkenberg-Knol EC, Meuwissen SG. Effect of short- and long-term treatment with omeprazole on the absorption and serum levels of cobalamin. Aliment Pharmacol Ther 1996;10:541–545.

    Article  CAS  PubMed  Google Scholar 

  4. Salom IL, Silvis SE, Doscherholmen A. Effect of cimetidine on the absorption of vitamin B12. Scand J Gastroenterol 1982;17:129–131.

    Article  CAS  PubMed  Google Scholar 

  5. Belaiche J, Cattan D, Zittoun J, Marquet J, Yvart J. Effect of ranitidine on cobalamin absorption. Dig Dis Sci 1983;28:667–668.

    Article  CAS  PubMed  Google Scholar 

  6. Streeter AM, Goulston KJ, Bathur FA, Hilmer RS, Crane GG, Pheils MT (1982) Cimetidine and malabsorption of cobalamin. Dig Dis Sci 21982;7:13–16.

    Article  Google Scholar 

  7. Steinberg WM, King CE, Toskes PP. Malabsorption of protein-bound cobalamin but not unbound cobalamin during cimetidine administration. Dig Dis Sci 1980;25:188–191.

    Article  CAS  PubMed  Google Scholar 

  8. Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol 2004;57:422–428.

    Article  PubMed  Google Scholar 

  9. Force RW, Meeker AD, Cady PS, Culbertson VL, Force WS, Kelley CM. Ambulatory care increased vitamin B12 requirement associated with chronic acid suppression therapy. Ann Pharmacother 2003;37:490–493.

    Article  CAS  PubMed  Google Scholar 

  10. Mitchell SL, Rockwood K. The association between antiulcer medication and initiation of cobalamin replacement in older persons. J Clin Epidemiol 2001;54:531–534.

    Article  CAS  PubMed  Google Scholar 

  11. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA 2013;310:2435–2442.

    Article  CAS  PubMed  Google Scholar 

  12. Cotter PE, O’Keefe ST. Use of proton pump inhibitors is not associated with vitamin B12 deficiency and in older hospital patients: A case control study. European Geriatric Medicine 2011;2:253–255.

    Article  Google Scholar 

  13. Jung SB, Nagaraja V, Kapur A, Eslick GD. Association between vitamin B12 deficiency and long-term use of acid-lowering agents: a systematic review and metaanalysis. Intern Med J 2015;45:409–416.

    Article  CAS  PubMed  Google Scholar 

  14. Grasbeck R, Kantero I, Siurala M. Influence of calcium ions on vitamin-B12 absorption in steatorrhoea and pernicious anaemia. Lancet 1959;1:234.

    Article  CAS  PubMed  Google Scholar 

  15. Gay JD, Grimes JD. Idiopathic hypoparathyroidism with impaired vitamin B 12 absorption and neuropathy. Can Med Assoc J 1972;107:54–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000;23:1227–1231.

    Article  CAS  PubMed  Google Scholar 

  17. Kozyraki R, Cases O. Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders. Biochimie 2013;95:1002–1007.

    Article  CAS  PubMed  Google Scholar 

  18. MacFarlane AJ, Greene-Finestone LS, Shi Y. Vitamin B-12 and homocysteine status in a folate-replete population: results from the Canadian Health Measures Survey. Am J Clin Nutr 2011;94:1079–1087.

    Article  CAS  PubMed  Google Scholar 

  19. Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP, Allen RH. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr 1994;60:2–11.

    CAS  PubMed  Google Scholar 

  20. Pennypacker LC, Allen RH, Kelly JP, Matthews LM, Grigsby J, Kaye K, Lindenbaum J, Stabler SP. High prevalence of cobalamin deficiency in elderly outpatients. J Am Geriatr Soc 1992;40:1197–1204.

    Article  CAS  PubMed  Google Scholar 

  21. Rajan S, Wallace JI, Beresford SA, Brodkin KI, Allen RA, Stabler SP. Screening for cobalamin deficiency in geriatric outpatients: prevalence and influence of synthetic cobalamin intake. J Am Geriatr Soc 2002;50:624–630.

    Article  PubMed  Google Scholar 

  22. Shahar A, Feiglin L, Shahar DR, Levy S, Seligsohn U. High prevalence and impact of subnormal serum vitamin B12 levels in Israeli elders admitted to a geriatric hospital. J Nutr Health Aging 2001;5:124–127.

    CAS  PubMed  Google Scholar 

  23. Dharmarajan TS, Ugalino JT, Kanagala M, Pitchumoni S, Norkus EP. Vitamin B12 status in hospitalized elderly from nursing homes and the community. J Am Med Dir Assoc 2000;1:21–24.

    CAS  PubMed  Google Scholar 

  24. O’Leary F, Flood VM, Petocz P, Allman-Farinelli M, Samman S. B vitamin status, dietary intake and length of stay in a sample of elderly rehabilitation patients. J Nutr Health Aging 2011;15:485–489.

    Article  PubMed  Google Scholar 

  25. Lachner C, Martin C, John D, Nekkalapu S, Sasan A, Steinle N, Regenold WT. Older adult psychiatric inpatients with non-cognitive disorders should be screened for vitamin B12 deficiency. J Nutr Health Aging 2014;18:209–212.

    Article  CAS  PubMed  Google Scholar 

  26. Institut national d’excellence en santé et en services sociaux (INESSS). Portrait de l’usage des inhibiteurs de la pompe à protons (IPP) chez les adultes assurés par le régime public d’assurance médicaments. ETMIS 2012;8:1–51.

    Google Scholar 

  27. Kergoat MJ, Latour J, Julien I, Plante MA, Lebel P, Mainville D, Bolduc A, Buckland JA. A discharge summary adapted to the frail elderly to ensure transfer of relevant information from the hospital to community settings: a model. BMC Geriatr 2010;10:69.

    Article  PubMed  PubMed Central  Google Scholar 

  28. de Jager J, Kooy A, Lehert P, Wulffele MG, van der Kolk J, Bets D, Verburg J, Donker AJ, Stehouwer CD. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ 2010;340:c2181.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Arendt JF, Nexo E. Cobalamin related parameters and disease patterns in patients with increased serum cobalamin levels. PLoS One 2012;7:e45979.

    Article  Google Scholar 

  30. Andres E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM 2013;106:505–515.

    Article  CAS  PubMed  Google Scholar 

  31. Mackenzie IL, Donaldson RM, Jr. Effect of divalent cations and pH on intrinsic factor-mediated attachment of vitamin B 12 to intestinal microvillous membranes. J Clin Invest 1972;51:2465–2471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Miyata S, Inada M. Effects of divalent cations on vitamin B12 adsorption to brush borders of rat intestine. J Nutr Sci Vitaminol (Tokyo) 1976;22:187–200.

    Article  CAS  Google Scholar 

  33. Cotter R, Rothenberg SP. Solubilization, partial purification and radioassay for the intrinsic factor receptor from the ileal mucosa. Br J Haematol 1962;34:477–487.

    Article  Google Scholar 

  34. Okuda K. Mucosal adsorption and absorption of vitamin B12 in the intestine of the rat. Proc Soc Exp Biol Med 1962;111:320–323.

    Article  CAS  PubMed  Google Scholar 

  35. Okuda K, Sasayama K. Effects of ethylenediaminetetraacetate and metal ions in intestinal absorption of vitamin B 12 in man and rats. Proc Soc Exp Biol Med 1965;120:17–20.

    Article  CAS  PubMed  Google Scholar 

  36. Herbert V. Studies on the role of intrinsic factor in vitamin B12 absorption, transport, and storage. Am J Clin Nutr 1959;7:433–443.

    CAS  PubMed  Google Scholar 

  37. Grasbeck R, Nyberg W. Inhibition of radiovitamin B12 absorption by ethylenediaminetetraacetate (EDTA) and its reversal by calcium ions. Scand J Clin Lab Invest 1958;10:448.

    Article  CAS  PubMed  Google Scholar 

  38. Wright MJ, Sullivan RR, Gaffney-Stomberg E, Caseria DM, O’Brien KO, Proctor DD, Simpson CA, Kerstetter JE, Insogna KL. Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: a randomized, crossover, controlled clinical trial. J Bone Miner Res 2010;25:2205–2211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hansen KE, Jones AN, Lindstrom MJ, Davis LA, Ziegler TE, Penniston KL, Alvig AL, Shafer MM. Do proton pump inhibitors decrease calcium absorption? J Bone Miner Res 2010;25:2786–2795.

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Marie-Jeanne Kergoat.

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Presse, N., Perreault, S. & Kergoat, MJ. Vitamin B12 deficiency induced by the use of gastric acid inhibitors: Calcium supplements as a potential effect modifier. J Nutr Health Aging 20, 569–573 (2016). https://doi.org/10.1007/s12603-015-0605-x

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  • DOI: https://doi.org/10.1007/s12603-015-0605-x

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