Metformin increases liver accumulation of vitamin B12 – An experimental study in rats

Aims/hypothesisPatients treated with metformin exhibit low levels of plasma vitamin B12 (B12), and are considered at risk for developing B12 deficiency. In this study, we investigated the effect of metformin treatment on B12 uptake and distribution in rats.MethodsSprague Dawley rats (n = 18) were divided into two groups and given daily subcutaneous injections with metformin or saline (control) for three weeks. Following this, the animals received an oral dose of radio-labeled B12 (57[Co]-B12), and urine and feces were collected for 24 h. Plasma, bowel content, liver, and kidneys were collected and analyzed for B12, unsaturated B12-binding capacity, and 57[Co]-B12.ResultsThree weeks of metformin treatment reduced plasma B12 by 22% or 289 [47-383] pmol/L (median and [range]) (p = 0.001), while no effect was observed on unsaturated B12-binding capacity. Compared with controls, the amount of B12 in the liver was 36% (p = 0.007) higher in metformin-treated rats, while the B12 content in the kidney was 34% (p = 0.013) lower. No difference in the total amount of absorbed 57[Co]-B12 present in the tissues and organs studied was found, suggesting that metformin has no decreasing effect on the B12 absorption.Conclusions/interpretationThese results show that metformin treatment increases liver accumulation of B12, thereby resulting in decreases in circulating B12 and kidney accumulation of the vitamin. Our data questions whether the low plasma B12 observed in patients treated with metformin reflects impaired B12 status, and rather suggests altered tissue distribution and metabolism of the vitamin.

► Three weeks of metformin treatment reduces plasma B12 in rats. ► Metformin increases vitamin B12 uptake and accumulation in the rat liver. ► Metformin did not decrease the absorption of vitamin B12 in rats.