Association of Biochemical B(12) Deficiency With Metformin Therapy and Vitamin B(12) Supplements: The National Health and Nutrition Examination Survey, 1999–2006

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.