(OR18-05-23) A Quantification of the Effect of Calcium Supplementation on Reversing Metformin-Based Inhibition of Vitamin B12 Bioavailability

Objectives: To quantify the impact of an oral calcium supplement on reversing the inhibition of vitamin B12 (B12) bioavailability by metformin.

Methods: B₁₂ bioavailability was measured using oral [¹³C]-cyanocobalamin (2.5 µg) in healthy subjects with normal B₁₂ status. Bioavailability was measured from a two-compartment model describing the kinetics of the plasma appearance of [¹³C]-methylcobalamin measurements at 5, 6 and 7 hours after tracer dosing, since the tracer was completely decyanated in the plasma. The measurement of bioavailability was made in the morning, in the fasted state, after the following acute treatments had been completed: metformin hydrochloride alone (M, 3 tablets of 850mg over the prior 16 hours), metformin plus calcium carbonate (MC, 500 mg tablets co-administered with metformin) or control (B, no intervention). These treatments were allocated in random order to each subject with one month intervening washout periods.

Results: Seven participants were studied: 3 male and 4 female. Metformin at this dose was well tolerated but one subject had gastritis with vomiting and withdrew from the study. The age and serum active B₁₂ concentrations (mean±SD) of the 7 participants was 20.4±1.7y and 47.9±18.3 pmol/L respectively. B₁₂ bioavailability was estimated as 42.6±10.2% in the B arm, reduced to 30.8±15.3% (B vs M, p=0.02, paired Wilcoxon) in the M arm and increased to 46.4±8.6% (B vs MC, p=0.13, paired Wilcoxon) in the MC arm.

Conclusions: Metformin significantly reduced B₁₂ bioavailability to 72% of its baseline value. When calcium supplements were added, the B₁₂ bioavailability returned to the baseline value in this paired analysis. This could be important in Indian populations who are predominantly vegetarian with low B₁₂ intakes, in whom diabetes is also prevalent. The role of high calcium foods along with metformin in the treatment of diabetes merits further study to prevent B₁₂ deficiency.

Funding Sources: DBT/ Wellcome Trust India Alliance