Management of Vitamin B12 Deficiency: What Is the Role of Oral Therapy?

To the Editor,

I read with interest the article by Ambareen Jan, BS, and R. Dobbin Chow, MD, FACP, from the March 2011 issue of Clinical Geriatrics.¹ Clinicians should be reminded that vitamin B₁₂ deficiency can also occur with the chronic use of the medication metformin for the treatment of type 2 diabetes,² and with the exposure of susceptible elderly patients to nitrous oxide during anesthesia.³

Metformin causes malabsorption of vitamin B₁₂ by competitive interference with the calcium-dependent vitamin B₁₂-intrinsic factor complex to ileal cell receptors.⁴ This process seems to be reversed with oral calcium supplementation.⁴ The mechanism for nitrous oxide is the oxidation of vitamin B₁₂ from the active cobalamin I form to the inactive cobalamin III form. This impairs the conversion of homocysteine to methionine, which is important for the methylation of myelin sheath proteins.^3,5 Therefore, elderly patients on metformin medication and/or who are scheduled for elective surgery should have their vitamin B₁₂ status evaluated and repleted, if necessary.

Andrew S. Chan, MD
Family Care Specialists Medical Group
White Memorial Medical Center
Los Angeles, CA

The author reports no relevant financial relationships.

References

1. Jan A, Chow RD. Management of vitamin B₁₂ deficiency: what is the role of oral therapy? Clinical Geriatrics. 2011;19(3):37-40.

2. de Jager J, Kooy A, Lehert P, et al. Long term treatment of metformin in patients with type 2 diabetes and risk of vitamin B12 deficiency: randomised placebo controlled trial. BMJ. 2010;340:c2181. doi:10.1136/bmj.c2181.

3. Marié RM, Le Biez E, Busson P, et al. Nitrous oxide anesthesia-associated myelopathy. Arch Neurol. 2000;57(3):380-382.

4. Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V. Increase intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care. 2000;23(9):1227-1231.

5. Cartner M, Sinnott M, Silburn P. Paralysis caused by “nagging.” Med J Aust. 2007;187(6):366-367.
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Dr. Chow responds:

While this was not the main focus of our article, we acknowledge that these two rare, but important, causes of vitamin B₁₂ deficiency should be included in a comprehensive listing of the causes of vitamin B₁₂ deficiency. We thank Dr. Chan for bringing these causes to our attention.

R. Dobbin Chow, MD, FACP
Program Director and Vice Chair of Medicine
Department of Medicine
Good Samaritan Hospital
Baltimore, MD