title: Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin.
abstract: OBJECTIVE
  Of patients who are prescribed metformin, 10-30% have evidence of reduced vitamin B12 absorption. B12-intrinsic factor complex uptake by ileal cell surface receptors is known to be a process dependent on calcium availability Metformin affects calcium-dependent membrane action. The objective of this study was to determine the magnitude and mechanism of the reduction in serum vitamin B12 after metformin administration.
  
  
  METHODS
  A comparative study design was employed using 2 groups (metformin and control). A total of 21 patients with type 2 diabetes received sulfonylurea therapy; 14 of these 21 patients were switched to metformin. Monthly serum total vitamin B12 measurements and holotranscobalamin (holoTCII) (B12-TCII) were performed. After 3 months of metformin therapy, oral calcium supplementation was administered.
  
  
  RESULTS
  Serial serum vitamin B12 determinations revealed a similar decline in vitamin B12 and holoTCII. Oral calcium supplementation reversed the metformin-induced serum holoTCII depression.
  
  
  CONCLUSIONS
  Patients receiving metformin have diminished B12 absorption and low serum total vitamin B12 and TCII-B12 levels because of a calcium-dependent ileal membrane antagonism, an effect reversed with supplemental calcium.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, USA. bauman.william@bronx.va.gov
authors.forename: W A
authors.initials: WA
authors.lastname: Bauman
authors.forename: S
authors.initials: S
authors.lastname: Shaw
authors.forename: E
authors.initials: E
authors.lastname: Jayatilleke
authors.forename: A M
authors.initials: AM
authors.lastname: Spungen
authors.forename: V
authors.initials: V
authors.lastname: Herbert
mesh_terms: D000328:Adult; D002119:Calcium Carbonate / Q000627:therapeutic use*; D002136:Calcium, Dietary / Q000627:therapeutic use*; D019587:Dietary Supplements; D005006:Ethnicity; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008687:Metformin / Q000009:adverse effects*; D008875:Middle Aged; D014805:Vitamin B 12 / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D002136:Calcium, Dietary; D007004:Hypoglycemic Agents; D008687:Metformin; D002119:Calcium Carbonate; D014805:Vitamin B 12