Association of Biochemical B12 Deficiency With Metformin Therapy and Vitamin B12 Supplements

Abstract

OBJECTIVETo describe the prevalence of biochemical B12 deficiency in adults with type 2 diabetes taking metformin compared with those not taking metformin and those without diabetes, and explore whether this relationship is modified by vitamin B12 supplements.RESEARCH DESIGN AND METHODSAnalysis of data on U.S. adults ≥50 years of age with (n = 1,621) or without type 2 diabetes (n = 6,867) from the National Health and Nutrition Examination Survey (NHANES), 1999–2006. Type 2 diabetes was defined as clinical diagnosis after age 30 without initiation of insulin therapy within 1 year. Those with diabetes were classified according to their current metformin use. Biochemical B12 deficiency was defined as serum B12 concentrations ≤148 pmol/L and borderline deficiency was defined as >148 to ≤221 pmol/L.RESULTSBiochemical B12 deficiency was present in 5.8% of those with diabetes using metformin compared with 2.4% of those not using metformin (P = 0.0026) and 3.3% of those without diabetes (P = 0.0002). Among those with diabetes, metformin use was associated with biochemical B12 deficiency (adjusted odds ratio 2.92; 95% CI 1.26–6.78). Consumption of any supplement containing B12 was not associated with a reduction in the prevalence of biochemical B12 deficiency among those with diabetes, whereas consumption of any supplement containing B12 was associated with a two-thirds reduction among those without diabetes.CONCLUSIONSMetformin therapy is associated with a higher prevalence of biochemical B12 deficiency. The amount of B12 recommended by the Institute of Medicine (IOM) (2.4 μg/day) and the amount available in general multivitamins (6 μg) may not be enough to correct this deficiency among those with diabetes.

Prevalence of vitamin B12 deficiency among individuals with type 2 diabetes mellitus in a South Indian rural community

“…4 Similarly, in a randomized controlled trial comparing insulin with metformin administered at a daily dose of 2.55g/day, the absolute risk of vitamin B12 deficiency was 7.2% higher in the metformin group than in the placebo group at the end of 4.3 years. 7,8 Our observation that vitamin B12 supplementation reduced the odds of its deficiency in patients with diabetes on metformin is similar to that reported in a prior cross sectional study. 6 Similarly, another study that analysed the National Health and Nutrition Examination Survey, USA (NHANES) data of adults aged ≥50 years reported a beneficial role for multivitamin supplementation containing vitamin B12 in a dose >6 mcg/day in individuals receiving metformin therapy.…”

“…Biochemical vitamin B12 deficiency was defined as serum vitamin B12 levels ≤ 200pg/ml. 7 Blood samples for complete blood picture-including haemoglobin, red blood cell(RBC) count, white blood cell count, platelet count, indices of RBC i.e., mean corpuscular volume(MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were assessed on an auto analyser (Mindray BC 3000plus). Glycosylated haemoglobin (HbA1c) was estimated by high performance liquid chromatography (Biorad D10).…”

Comparison of two methods for measuring methylmalonic acid as a marker for vitamin B12 deficiency

“…One further diagnostic role for MMA is in patients with diabetes type 2 treated with metformin. Circulating serum vitamin B12 levels (holoTC and total B12) are low in metformintreated patients [22,23]. Metformin has long been thought to cause vitamin B12 deficiency [24].…”

Use of Metformin for Cardiometabolic Risks in Psychiatric Practice: Need-to-Know Safety Issues

“…Whereas the intake of daily oral B 12 -containing supplements may reduce the risk of B 12 deficiency, 19,20 there is no assurance that this strategy would prove effective, particularly when diabetes is present. 20 Alternately, supplementation with oral calcium may attenuate metformin-associated impairment in B 12 absorption 21 ; however, unless otherwise indicated (as in postmenopausal women), advising calcium supplementation adds to the complexity of the patient's prescription and can result in medication errors and problems in treatment adherence.…”

“…20 Alternately, supplementation with oral calcium may attenuate metformin-associated impairment in B 12 absorption 21 ; however, unless otherwise indicated (as in postmenopausal women), advising calcium supplementation adds to the complexity of the patient's prescription and can result in medication errors and problems in treatment adherence.…”