title: Association of biochemical B₁₂ deficiency with metformin therapy and vitamin B₁₂ supplements: the National Health and Nutrition Examination Survey, 1999-2006.
abstract: 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.
  
  
  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.
authors.affiliation: Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
authors.forename: Lael
authors.initials: L
authors.lastname: Reinstatler
authors.forename: Yan Ping
authors.initials: YP
authors.lastname: Qi
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Williamson
authors.forename: Joshua V
authors.initials: JV
authors.lastname: Garn
authors.forename: Godfrey P
authors.initials: GP
authors.lastname: Oakley
mesh_terms: D000368:Aged; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D008297:Male; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D014805:Vitamin B 12 / Q000627:therapeutic use*; D014806:Vitamin B 12 Deficiency / Q000139:chemically induced* / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D008687:Metformin; D014805:Vitamin B 12