EBM Consult

Medications Known to Decrease Vitamin B12 Levels

Summary:

  • As summarized in the table provided, vitamin B12 (cobalamin) absorption and utilization by the body can be compromised with the chronic use of certain medications which include: colchicine, chloramphenicol, ethanol, histamine 2 receptor antagonists (H2RA), metformin, and proton pump inhibitors (PPI).
  • The chronic use of any of these medications has the potential to cause complications related to vitamin B12 deficiency, which includes impaired DNA synthesis, impaired cell division, hematopoiesis, hyperhomocysteinemia, and metabolism of odd-chain fatty acids that is necessary in preventing demyelination of nerves.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Last Reviewed: October 2015

Explanation

  • It is now known that some medications, when used chronically, can result in undesirable side effects that were not necessarily obvious or present within most initial clinical trials.  A delayed adverse drug effect or interaction could easily occur with vitamin B12 since the time necessary for most patients to become deficient can be delayed one or more years due to high storage levels in the body.  The table below summarizes common medications that have been associated with reducing the levels of vitamin B12 as well as the proposed mechanism for this interaction.1-12   The order of listed medications is alphabetical and not reflective of severity or level of importance. 

                                   

    The chronic use of any of these medications has the potential to cause complications related to vitamin B12 deficiency, which includes impaired DNA synthesis, impaired cell division, hematopoiesis, hyperhomocysteinemia, and metabolism of odd-chain fatty acids that is necessary in preventing demyelination of nerves.  As discussed in other articles in the database, the use of antacids seem to only impair protein bound vitamin B12 ingested from animal derived dietary sources.

    References:

    1. National Institutes of Health. Office of Dietary Supplements.  Dietary Supplement Fact Sheet: Vitamin B12.  Bethesda, Maryland.  05/26/2010. 
    2. Stopa EG, O'Brien R, Katz M.  Effect of colchicine on guinea pig intrinsic factor-vitamin B12 receptor.  Gastroenterology  1979;76:309-14.  
    3. Palopoli JJ, Waxman J.  Colchicine neuropathy or vitamin B12 deficiency neuropathy?  N Eng J Med  1987;317:1290-1.  
    4. Kittang E, Aadland E, Schjonsby H.  Effect of omeprazole on the secretion of intrinsic factor, gastric acid and pepsin in man.  Gut  1985;26:594-8.  
    5. Force RW, Nahata MC.  Effect of histamine H2-receptor antagonists on vitamin B12 absorption.  Ann Pharmacother 1992;26:1283-6. 
    6. Ruscin JM, Page RL 2nd, Valuck RJ.  Vitamin B(12) deficiency associated with histamine (2)-receptor antagonists and a proton-pump inhibitor.  Ann Pharmacother  2002;36:812-6.  
    7. Bauman WA, Shaw S, Jayatilleke K et al. Increased intake of calcium reverses the B12 malabsorption induced by metformin. Diabetes Care 2000;23:1227-31.
    8. de Jager J, Kooy A, Lehert P et al. 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.
    9. Saltzman JR, Kemp JA, Golner BB et al.  Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption.  J Am Coll Nutr 1994;13:584-91.
    10. Schenk BE, Festen HP, Kuipers EJ et al.  Effect of short- and long-term treatment with omeprazole on the absorption and serum levels of cobalamin.  Aliment Pharmacol Ther 1996;10:541-5.
    11. Bradford GS, Taylor CT.  Omeprazole and vitamin B12 deficiency.  Ann Pharmacother  1999;33:641-3.
    12. Bellou A, Aimone-Gastin I, De Korwin JD et al.  Cobalamin deficiency with megaloblastic anaemia in one patient under long-term omeprazole therapy.  J Intern Med 1996;240:161-4.

MESH Terms & Keywords

  • Vitamin B12 Levels, Cobalamin, B12, Colchicine, PPI, Proton Pump Inhibitors, Metformin, Glucophage, Chloramphenicol