JDM  Vol.2 No.1 , February 2012
Methylmalonic acid as an indicator of vitamin B12 deficiency in patients on metformin
Abstract: Context: Metformin is frequently prescribed for the treatment of type 2 diabetes mellitus. It is recommended as a first line agent by the American Diabetes Association. Vitamin B12 deficiency has been suggested as a side effect of metformin therapy; however, previous studies have not assessed the utility of methylmalonic acid levels as an indicator of vitamin B12 status. Objective: To investigate the prevalence of vitamin B12 deficiency in patients on metformin therapy for diabetes by utilizing both vitamin B12 and methylmalonic acid levels. Design, Setting, and Patients: Eighty-eight patients with diabetes, who were either on or off metformin therapy for at least thirty days, were enrolled in a case-controlled study. Blood work and questionnaires were used for analysis. Main Outcome Measures Study: Aims were to detect a clinically significant difference in the prevalence of vitamin B12 deficiency between metformin users and non-users, where such deficiency is defined by both low vitamin B12 and elevated methylmalonic acid levels. Results: Two Sample Equal Variance T-Tests were used to compare averages of measured values and the Chisquare test was used to determine the significance of calculated vitamin B12 deficiency rates between the two groups of patients. Two separate methods for defining vitamin B12 deficiency were utilized. There was no difference in the prevalence of vitamin B12 deficiency in metformin users compared with non-users by either method. Average homocysteine levels were higher in those not on metformin therapy. Conclusion: Vitamin B12 deficiency as defined by an elevated methylmalonic acid level was no greater in patients with diabetes on metformin therapy versus those patients not on metformin treatment.
Cite this paper: Shtaynberg, N. , Singh, M. , Sohn, P. , Goldman, M. and Cohen, N. (2012) Methylmalonic acid as an indicator of vitamin B12 deficiency in patients on metformin. Journal of Diabetes Mellitus, 2, 72-75. doi: 10.4236/jdm.2012.21011.

[1]   Centers for Disease Control and Prevention (CDC) (2009) Diabetes: Successes and opportunities for population-based prevention and control: At a glance 2009.

[2]   Tompkins, G.H., Hadden, D.R., Weaver, J.A., et al. (1971) Vitamin B12 status of patients on long-term metformin therapy. British Medical Journal (BMJ), 2, 685-687. doi:10.1136/bmj.2.5763.685

[3]   Adams, J.F., Clark, J.S., Ireland, J.T., et al. (1983) Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy. Diabetologia, 24, 16-18. doi:10.1007/BF00275941

[4]   Wulffelé, M.G., Kooy, A., Lehert, P., et al. (2003) Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: A randomized, placebo-controlled trial. Journal of Internal Medicine, 254, 455-463. doi:10.1046/j.1365-2796.2003.01213.x

[5]   Hoogeveen, E.K., Kostense, P.J., Jakobs, C., et al. (1997) Does metformin increase the serum total homocysteine level in non-insulin-dependent diabetes mellitus? Journal of Internal Medicine, 242, 389-394. doi:10.1046/j.1365-2796.1997.00231.x

[6]   Savage, D.G., Lindenbaum, J., Stabler, S.P. and Allen, R.H. (1994) Sensitivity of serum methylmalonic acid and total homocysteine determinants for diagnosing cobalamin and folate deficiencies. American Journal of Medicine, 96, 239-246. doi:10.1016/0002-9343(94)90149-X

[7]   Lindenbaum, J., Savage, D.G., Stabler, S.P. and Allen, R.H. (1990) Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. American Journal of Hematology, 34, 99-107. doi:10.1002/ajh.2830340205

[8]   Ting, R.Z., Szeto, C.C., Chan, M.H., et al. (2006) Risk factors of vitamin B(12) de?ciency in patients receiving metformin. Archives of Internal Medicine, 166, 1975-1979. doi:10.1001/archinte.166.18.1975

[9]   Pongchaidecha, M., Srikusalanukul, V., Chattananon, A., et al. (2004) Effect of metformin on plasma homocysteine, vitamin B12 and folic acid: a cross-sectional study in patients with type 2 diabetes mellitus. Journal of the Medical Association of Thailand, 87, 780-787.

[10]   Carlsen, S.M., Kjotrod, S., Vanky, E., et al. (2007) Homocysteine levels are unaffected by metformin treatment in both nonpregnant and pregnant women with polycystic ovary syndrome. Acta Obstetricia et Gynecologica Scandinavica, 86, 145-150. doi:10.1080/00016340600855946

[11]   Sahin, M., Tutuncu, N.B., Ertugrul, D., et al. (2007) Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. Journal of Diabetes and Its Complications, 21, 118-123. doi:10.1016/j.jdiacomp.2005.10.005