Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin

W. A. Bauman, S. Shaw, E. Jayatilleke, A. M. Spungen, V. Herbert

Research output: Contribution to journalArticlepeer-review

300 Scopus citations


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. RESEARCH DESIGN AND 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 holo TCII. 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.

Original languageEnglish
Pages (from-to)1227-1231
Number of pages5
JournalDiabetes Care
Issue number9
StatePublished - 2000
Externally publishedYes


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