Publications

BACKGROUND & AIMS: Metformin is a widely prescribed first line drug for the treatment of type 2 diabetes mellitus (DM). Studies have shown that the use of  metformin is often associated with a decrease in vitamin B(12) (B(12)) levels in  patients with DM. Few studies have shown that this effect could be mitigated with  calcium supplementation. In the present study, we quantified the effect of  metformin, and metformin co-administered with calcium on B(12) absorption using a  novel stable isotope [(13)C] cyanocobalamin tracer. METHODS: A pilot crossover  study was conducted to estimate the bioavailability of B(12) in healthy subjects,  using [(13)C] cyanocobalamin as a tracer. In the study, [(13)C] cyanocobalamin  was administered orally to the participants followed by hourly venous sampling to  measure the concentration of the tracer and estimate bioavailability. This  protocol was followed for three experiment days, each separated by a one month  wash out period. As part of the study, all participants received the tracer alone  for the control day (C), metformin 850 mg along with the tracer for the metformin  day (M) and metformin 850 mg with calcium 500 mg and the tracer for the metformin  calcium day (MC). RESULTS: Seven participants completed all three experiment  days. The mean B(12) bioavailability (±SD, n = 7) was 42.6 ± 10.2% for the  control day (C), 30.8 ± 15.3% for the metformin day (M) and 46.4 ± 8.6% for the  metformin-calcium day (MC). Repeated measures ANOVA was done and the pairwise  comparison showed a significant difference in the B(12) bioavailability between  control and metformin day (C vs M p = 0.010), and between the metformin and  metformin with calcium day (M vs MC p = 0.003). CONCLUSION: B(12) bioavailability  reduced significantly from baseline (C) when metformin (M) was administered and  this reduction was reversed when calcium was co-administered (MC) in healthy  participants. In patients using metformin, calcium supplementation as a strategy  to prevent B(12) deficiency needs to be further studied.