Increased intake of calcium reverses vitamin B₁₂ malabsorption induced by metformin

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.