Metformin causing vitamin B12 deficiency: a guilty verdict without sufficient evidence.

Metformin causing vitamin B12 (B12) deficiency has become a traditional myth in medical literature (1,2). But what evidence do we have? The possibility to measure holotranscobalamin (active B12) and the metabolic marker, methylmalonic acid (MMA), has changed the practice of diagnosing B12 deficiency in recent years. We have learned that not all low plasma B12 means a “deficiency” and not all high plasma B12 mean “sufficiency.” When B12 is internalized and is able to maintain the B12dependent intercellular enzyme activities (methionine synthase and methylmalonyl-CoA mutase), plasma total homocysteine (tHcy) andMMAwill be within the reference range. This revolution in diagnosing B12 deficiency has provided convincing evidence that metformin is not as bad as its reputation.