Metformin is a widely prescribed medication for individuals with type 2 diabetes. It works by decreasing glucose production in the liver, reducing glucose absorption from the digestive tract, and enhancing the body’s sensitivity to insulin. Long-term metformin use is associated with a potential decrease in vitamin B12 levels. Vitamin B12, also known as cobalamin, is a water-soluble vitamin that plays a role in nerve cell development, red blood cell formation, and DNA synthesis.
How Metformin Affects Vitamin B12 Levels
Metformin’s effect on vitamin B12 levels is a recognized side effect, though precise mechanisms are still being investigated. One proposed mechanism involves metformin interfering with the calcium-dependent absorption of the intrinsic factor-vitamin B12 complex in the small intestine. Metformin may impart a positive charge to the cubilin receptor, hindering vitamin B12 uptake.
Another theory suggests metformin can alter small intestine motility, potentially leading to small intestinal bacterial overgrowth. This overgrowth might inhibit vitamin B12 absorption. Changes in bile acid metabolism and reabsorption, or reduced intrinsic factor secretion, have also been suggested as contributing factors. Not all individuals taking metformin will experience a vitamin B12 deficiency, but the risk can increase with higher doses and longer treatment durations.
Recognizing Vitamin B12 Deficiency
Vitamin B12 deficiency symptoms can develop gradually and worsen if left unaddressed. Neurological symptoms are common and include numbness, tingling sensations (“pins and needles”), difficulty walking due to loss of physical coordination (ataxia), dizziness, and muscle weakness. Cognitive issues such as memory problems, confusion, difficulty concentrating, and even personality changes or depression may also arise.
Beyond neurological effects, individuals might experience hematological symptoms, primarily related to anemia. These can manifest as extreme tiredness, general weakness, pale or yellowish skin, and shortness of breath. Other general symptoms can include a sore and red tongue (glossitis), loss of appetite, and weight loss. If a deficiency is suspected, it is diagnosed through blood tests, which include measuring serum B12 levels. In cases where serum B12 levels are borderline, additional markers like methylmalonic acid (MMA) and homocysteine may be tested, as elevated levels of both suggest a vitamin B12 deficiency, even if serum B12 appears normal.
Managing and Preventing Deficiency
For individuals on long-term metformin therapy, regular monitoring of vitamin B12 levels is recommended. Healthcare providers may check serum B12 levels, especially if symptoms emerge or if other risk factors are present. These risk factors include being 65 years or older, following a strict vegan or vegetarian diet, or taking acid-reducing medications like proton pump inhibitors.
Strategies can help prevent or manage vitamin B12 deficiency while taking metformin. Dietary sources of vitamin B12 are primarily found in animal products such as meat, seafood, poultry, and dairy. Fortified foods like certain breakfast cereals and plant-based milks also offer a source.
If dietary intake is insufficient or a deficiency is confirmed, oral vitamin B12 supplements, such as cyanocobalamin or methylcobalamin, can be effective. In some instances, particularly for severe deficiencies or malabsorption issues, vitamin B12 injections (e.g., 1 mg of hydroxocobalamin every three months) may be recommended. It is important to consult a healthcare professional for personalized advice regarding monitoring, dietary adjustments, and appropriate supplementation, as they can determine the best course of action based on individual needs and health status.