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Diabetes Care. 2012 Feb;35(2):327-33. doi: 10.2337/dc11-1582. Epub 2011 Dec 16.

Association of biochemical B₁₂ deficiency with metformin therapy and vitamin B₁₂ supplements: the National Health and Nutrition Examination Survey, 1999-2006.

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Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.



To describe the prevalence of biochemical B(12) deficiency in adults with type 2 diabetes taking metformin compared with those not taking metformin and those without diabetes, and explore whether this relationship is modified by vitamin B(12) supplements.


Analysis of data on U.S. adults ≥50 years of age with (n = 1,621) or without type 2 diabetes (n = 6,867) from the National Health and Nutrition Examination Survey (NHANES), 1999-2006. Type 2 diabetes was defined as clinical diagnosis after age 30 without initiation of insulin therapy within 1 year. Those with diabetes were classified according to their current metformin use. Biochemical B(12) deficiency was defined as serum B(12) concentrations ≤148 pmol/L and borderline deficiency was defined as >148 to ≤221 pmol/L.


Biochemical B(12) deficiency was present in 5.8% of those with diabetes using metformin compared with 2.4% of those not using metformin (P = 0.0026) and 3.3% of those without diabetes (P = 0.0002). Among those with diabetes, metformin use was associated with biochemical B(12) deficiency (adjusted odds ratio 2.92; 95% CI 1.26-6.78). Consumption of any supplement containing B(12) was not associated with a reduction in the prevalence of biochemical B(12) deficiency among those with diabetes, whereas consumption of any supplement containing B(12) was associated with a two-thirds reduction among those without diabetes.


Metformin therapy is associated with a higher prevalence of biochemical B(12) deficiency. The amount of B(12) recommended by the Institute of Medicine (IOM) (2.4 μg/day) and the amount available in general multivitamins (6 μg) may not be enough to correct this deficiency among those with diabetes.

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