Metformin and B12 Deficiency: How Are They Connected?

Key Takeaways

Vitamin B12 deficiency is a common side effect in metformin-treated diabetic patients. The risk is higher if you take a higher or long-term dose. The risk is also higher in people taking medications such as proton pump inhibitors for acid reflux.
Different studies have reported a wide variation in the prevalence of vitamin B12 deficiency in metformin users, with incidence ranging from 6% to 50%.
Metformin-treated patients may need to take vitamin B12 supplementation if they have inadequate dietary intake of vitamin B12, low serum concentrations of vitamin B12, or high serum homocysteine levels.

Metformin is an oral antidiabetic drug that is widely used to control high blood sugar levels and increase insulin resistance in people with Type 2 diabetes mellitus. This medication is also used off-label to treat polycystic ovary syndrome. However, high daily metformin doses and long-term metformin therapy can increase the risk of serum vitamin B12 deficiency in some cases. Please continue reading to find out more about B12 deficiency in metformin users.

What are the symptoms of lack of B12?

Vitamin B12 (cobalamin) is an essential nutrient. Symptoms of vitamin B12 (cobalamin) deficiency include weakness, tiredness, headaches, numbness, tingling (pins and needles sensation), shortness of breath, palpitations, mouth ulcers, indigestion, nausea, diarrhea, loss of appetite, and cognitive impairment.

Causes of vitamin B12 deficiency include food cobalamin malabsorption (low intestinal absorption of the vitamin from food) due to intrinsic factor receptor deficiency (a substance needed for absorption of B12), impaired calcium availability, gastrointestinal disorders such as chronic gastritis, Crohn’s disease, and other bowel inflammatory disorders, surgery on the digestive tract such as total or partial gastrectomy, or autoimmune conditions.

Risk factors for vitamin B12 deficiency include older age, strict vegetarian diets, and side effects of some medications.

Does metformin therapy cause vitamin B12 deficiency?

Vitamin B12 deficiency is a potential side effect in metformin-treated diabetic patients. The risk of metformin-associated vitamin B12 deficiency is increased in people taking a higher daily metformin dose, those on long-term metformin treatment, those with other risk factors for vitamin B12 deficiency, and people taking certain other medications such as proton pump inhibitors.

Patients receiving metformin are instructed by their healthcare providers to check their vitamin B12 levels periodically during metformin treatment, especially if it is a longer treatment duration or higher metformin dose. Healthcare providers typically consider individual patient factors, symptoms, and the duration of metformin therapy when deciding on the frequency of monitoring. Blood tests to check for vitamin B12 or folate deficiency should also be done if any symptoms develop during metformin use.

How common is B12 deficiency with metformin treatment?

There is a wide variation in the reported prevalence of vitamin B12 deficiency in metformin users. Different studies have reported an incidence ranging from 6% to 50%.

What happens when a diabetic has a B12 deficiency?

When a diabetic has B12 deficiency, they are at an increased risk of developing new or worsening symptoms of peripheral neuropathy (nerve damage). Both diabetes and vitamin B12 deficiency can cause this condition. Studies have found that approximately 6 out of 10 patients with diabetic peripheral neuropathy have low vitamin B12 levels.

Symptoms of peripheral neuropathy include weakness, numbness, tingling, and paresthesias (burning, prickling, or itching sensations) in the hands, feet, arms, and legs.

Should you take vitamin B12 if you take metformin?

Patients taking metformin do not necessarily need to take vitamin B12 supplementation. Most people can obtain enough vitamin B12 from food sources such as dairy products, eggs, poultry, fish, meat, and fortified foods. However, metformin-treated patients may need to take vitamin B12 supplementation if they have:

Inadequate dietary intake of vitamin B12.
Existing risk factors such as higher metformin doses or longer-term metformin therapy.
Low serum concentrations of vitamin B12.
High serum homocysteine levels (vitamin B12 breaks down homocysteine in the body).

Seek medical advice if you are on metformin treatment, especially a higher metformin dose or long-term metformin therapy, or if you have new or worsening symptoms of diabetic neuropathy.

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