Metformin can cause vitamin B12 deficiency by reducing the absorption of vitamin B12 from the gastrointestinal tract.

6% to 30% of people on metformin treatment have been reported to be deficient in vitamin B12, and vitamin B12 levels are inversely associated with the duration and dose of metformin treatment. The American Diabetes Association advises regular monitoring of vitamin B12 levels in diabetic patients taking metformin. Homocysteine ​​is an essential component of the one-carbon pathway of methionine metabolism, which plays a vital role in DNA methylation and many intracellular reactions of vitamin B12. Therefore, an elevation in homocysteine ​​is often due to vitamin B12 deficiency; several studies have focused on an increase in homocysteine ​​in people taking metformin. It is medically advisable to check that vitamin B12 deficiency does not occur under treatment with metformin.

Less meat is eaten in Asian countries, which suggests an increased risk of vitamin B12 deficiency. However, few studies have examined the effect of duration and dose of metformin use in the Asian population. Therefore, this study explored the prevalence of vitamin B12 deficiency in Korean patients with type 2 diabetes on long-term treatment with metformin. In addition, the study examined whether metformin-induced vitamin B12 deficiency in serum could reveal tissue deficiency by assessing serum homocysteine ​​levels.

The study protocol followed the ethical guidelines of the Declaration of Helsinki and received the support of the institutional review committee of Yongin Severance Hospital. All study participants gave their written consent. Cross-sectional research looked at people with type 2 diabetes on metformin treatment for at least six months. People with a medical history of gastrectomy, colectomy, inflammatory bowel disease, or pernicious anemia were not allowed to participate in the study. People with acute illnesses such as severe infection, cancer or acute coronary syndrome, significant organ damage in the past 90 days were not allowed to participate in the study. Vegetarian patients, pregnant women, and patients with blood disorders other than anemia were also not included in the study. One thousand one hundred and eleven patients aged 20 to 85 years participated in the study, 645 male patients.

All study participants took a baseline blood test and quizzes on neuropathy supplements, history of drug abuse, smoking habits, and alcohol use. Medical researchers carefully reviewed the medical records of patients. Blood and urine samples were taken on an empty stomach to assess serum vitamin B12, serum folic acid, serum homocysteine, glucose, insulin, HBA1C, hemoglobin, MCV, l ‘AST, ALT, creatine, total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol and urine creatine albumin ratio. The daily dose of metformin was determined as the average dose taken over the past six months. Competitive binding of enzyme-linked immunosorbent assays using a Unicel DxI analyzer of specified levels of vitamin B12. For the study, a serum B12 level of less than 300 pg / ml is deficient in vitamin B12.

Less than 1/3 of the patients were vitamin B12 deficient, with an average vitamin B12 level of 231.2 ± 44.8 pg / ml. Only one patient had a B12 level below 100 pg / ml in the participant group, and sixty patients had B12 levels below 200 pg / ml. Serum homocysteine ​​was much more significant in the B12 deficient group. Serum vitamin B12 levels were negatively correlated with metformin dose; however, they were not significantly related to the use of metformin. As the dose of metformin increased, serum vitamin B12 levels decreased dramatically. Finally, serum vitamin B12 levels demonstrated a negative relationship with homocysteine ​​levels, even after adjusting for several confounding factors such as age, sex, duration of diabetes, alcohol consumption, smoking , anemia, GFR and multivitamin supplementation. Metformin at ≥ 1500mg / d could be a major cause of vitamin B12 deficiency. Simultaneous multivitamin supplementation may protect against vitamin B12 deficiency. Serum homocysteine ​​is negatively associated with vitamin B12 levels. Thus, a deficiency correlated with the use of metformin can occur at the tissue level.

Practice the beads:

• Long-term use of metformin can lead to vitamin B12 deficiency.
• More research is needed to understand the mechanism by which metformin lowers vitamin B12 levels; however, the most likely hypothesis remains that metformin interferes with the calcium-dependent membrane action responsible for the absorption of the intrinsic factor of vitamin B12, which occurs in the terminal ileum.
• Patients on metformin treatment should check their B12 levels regularly, potentially once a year, to make sure they are within the normal range.

Kim, J., Ahn, CW, Fang, S., Lee, HS, & Park, JS (2019, November). Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes. Journal of Medicine.

Emmanuella Louissaint, PharmD candidate, Faculty of Pharmacy LECOM