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
Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12). Ann Intern Med 1994;120:211–215.
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.
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.
Salom IL, Silvis SE, Doscherholmen A. Effect of cimetidine on the absorption of vitamin B12. Scand J Gastroenterol 1982;17:129–131.
Belaiche J, Cattan D, Zittoun J, Marquet J, Yvart J. Effect of ranitidine on cobalamin absorption. Dig Dis Sci 1983;28:667–668.
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.
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.
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.
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.
Mitchell SL, Rockwood K. The association between antiulcer medication and initiation of cobalamin replacement in older persons. J Clin Epidemiol 2001;54:531–534.
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.
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.
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.
Grasbeck R, Kantero I, Siurala M. Influence of calcium ions on vitamin-B12 absorption in steatorrhoea and pernicious anaemia. Lancet 1959;1:234.
Gay JD, Grimes JD. Idiopathic hypoparathyroidism with impaired vitamin B 12 absorption and neuropathy. Can Med Assoc J 1972;107:54–56.
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.
Kozyraki R, Cases O. Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders. Biochimie 2013;95:1002–1007.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Arendt JF, Nexo E. Cobalamin related parameters and disease patterns in patients with increased serum cobalamin levels. PLoS One 2012;7:e45979.
Andres E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM 2013;106:505–515.
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.
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.
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.
Okuda K. Mucosal adsorption and absorption of vitamin B12 in the intestine of the rat. Proc Soc Exp Biol Med 1962;111:320–323.
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.
Herbert V. Studies on the role of intrinsic factor in vitamin B12 absorption, transport, and storage. Am J Clin Nutr 1959;7:433–443.
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.
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.
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.
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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