Why Metformin Users Need to Pay Attention to Vitamin B12

While not indicated to treat polycystic ovary syndrome (PCOS), metformin is the most commonly prescribed medication to help women suffering from the condition.  Alarming new research is showing a relationship between long-term metformin use and vitamin B12 deficiency, yet most health care providers rarely check B12 status in metformin users. A lack of vitamin B12 can result in serious and permanent neurological and nerve damage. Here’s what to know about vitamin B12 if you take metformin.

Metformin works as an insulin-sensitizer to reduce your production of glucose and is commonly prescribed to individuals with type 2 diabetes for this reason. Other names for metformin include glucophage, glucophage XR, glumetza, and fortamet.

Metformin lowers blood glucose and insulin levels in several ways: It suppresses the liver's production of glucose, increases the sensitivity of your liver, muscle, fat, and cells to the insulin your body makes, and decreases the absorption of carbohydrates you consume.

Metformin has been shown to improve insulin as well as lipid levels (cholesterol) in women with PCOS and may help improve ovulation.

Diabetes Prevention Program Outcomes Study (DDPOS) represents one of the largest and longest studies of metformin treatment available. A new analysis of the DDPOS published in the Journal of Clinical Endocrinology and Metabolism looked at B12 levels of individuals with prediabetes who took 850 mg Metformin twice daily and compared them to those taking a placebo. Vitamin B12 levels were assessed at 5 and 13 years.

Results from the DDPOS showed that long-term metformin use increased the risk for vitamin B12 levels. At 5 years, 5.2 percent of the metformin users had low serum B12 levels. At 13 years, 9.2 percent of metformin users had low B12 levels. When controlling for age, sex, and BMI, there was a 13 percent increased risk of B12 deficiency for each year of total metformin use.

It is believed that metformin can affect the absorption of vitamin B12 in the ileum of the small intestine. Not only were vitamin B12 levels affected in the DDPOS study, but homocysteine levels, a marker of cardiovascular risk, were increased over time in metformin users.

Other studies have shown that metformin can affect levels of vitamin B12 in as little as three months of use. A systematic review and meta-analysis looked at individuals with type 2 diabetes and women with PCOS who took metformin. Their results found the higher the metformin dose, the more deficient people were in vitamin B12 and that metformin reduced vitamin B12 levels in both long (≥3 years) and short (<3 years) term use.

The average dose of metformin for women with PCOS is 1,500 mg to 2,000 mg daily. The majority of women with PCOS take high doses of metformin for long-term use, increasing their risk for a vitamin B12 deficiency.

A water soluble vitamin, B12 is essential for nerve conduction, mental functioning, DNA synthesis, and red blood cell formation. Vitamin B12 is primarily found in animal products. Those who follow vegan diets must supplement their diets with vitamin B12. The recommended daily amount of vitamin B12 for most adults is 2.4 mcg.

Symptoms of B12 deficiency include certain types of anemia, neuropathy (nerve damage), chronic fatigue, memory loss, confusion, mood changes and even dementia.

A deficiency of vitamin B12 is very serious, affecting mood and energy and can result in permanent and irreversible neuropathy. Sometimes taking a multivitamin that has vitamin B12 can still result in a deficiency in metformin users. Individuals who take metformin should have their vitamin B12 levels assessed annually and supplement their diets as appropriate for them. The methylcobalamin type of vitamin B12 in a sublingual form (under the tongue) is best absorbed by the body.

A blood sample can assess levels of vitamin B12. It has been suggested that lab reference ranges for normal B12 levels are set too low and that symptoms of a deficiency can show up in levels under 400 pg/ml.

Checking methylmalonic acid (MMA) is a sensitive test that can more accurately reflect vitamin B12 status.

Bottom line: If you take metformin, ask your doctor to check your vitamin B12 levels annually and supplement your diet with vitamin B12 to prevent complications of a deficiency.