Several widely prescribed medications can lower your vitamin B12 levels over time, sometimes enough to cause deficiency. The most well-documented culprits are metformin (used for type 2 diabetes), acid-suppressing heartburn drugs, and certain seizure medications. Less common but clinically important causes include nitrous oxide, colchicine, and aminosalicylic acid.
Metformin
Metformin is the most commonly cited medication linked to B12 deficiency. About 30% of people on long-term metformin treatment develop some degree of B12 malabsorption. The drug interferes with a specific step in how B12 gets into your cells: normally, B12 binds to a protein called intrinsic factor in the stomach, and that complex relies on calcium to attach to receptors in the lower part of the small intestine. Metformin appears to alter the electrical charge on cell membranes, displacing calcium and disrupting this process.
The risk increases with higher doses and longer duration of use. The American Diabetes Association’s 2025 Standards of Care recommend periodic B12 testing for people taking metformin, particularly those who develop anemia or tingling and numbness in their hands or feet. No specific testing interval is defined, but the recommendation signals that this is a real and recognized concern rather than a theoretical one.
Heartburn and Acid Reflux Medications
Proton pump inhibitors (like omeprazole and pantoprazole) and H2 blockers (like famotidine) work by reducing stomach acid production. That same acid is needed to release B12 from the proteins in food, so suppressing it can gradually impair B12 absorption. Studies have found that taking either type of acid-suppressing medication daily for a year or more increases the risk of B12 deficiency.
This is particularly relevant because many people take these drugs for years, sometimes without a clear plan to reassess whether they’re still needed. If you’ve been on a heartburn medication for more than 12 months, it’s reasonable to have your B12 levels checked.
Seizure Medications
Several antiepileptic drugs, including carbamazepine, phenytoin, valproate, and lamotrigine, have been shown to significantly lower both folate and B12 levels during treatment. The mechanisms vary by drug. Phenytoin, for instance, competes with folate for binding sites on intestinal cells and speeds up the liver’s breakdown of folate. Carbamazepine similarly ramps up liver enzyme activity that metabolizes these vitamins faster than normal.
Because folate and B12 work together in key metabolic pathways, a drop in one can compound the effects of a drop in the other. Researchers have noted that these vitamin changes may affect the risk of secondary cardiovascular events in people with epilepsy, making monitoring especially important for long-term users.
Nitrous Oxide
Nitrous oxide, used both as a dental anesthetic and recreationally (sometimes called “whippets” or “laughing gas”), doesn’t just lower B12 levels. It permanently destroys the active form of the vitamin by oxidizing its cobalt atom, which irreversibly shuts down an enzyme called methionine synthetase. This blocks the body’s ability to produce methionine, a building block needed for DNA synthesis and for maintaining the protective coating around nerve fibers.
Even a single prolonged exposure can trigger problems in someone whose B12 is already borderline. Repeated recreational use can cause a serious condition called subacute combined degeneration of the spinal cord, leading to loss of position sense, weakness, and spasticity. This is one of the more dramatic examples of drug-induced B12 problems because the damage can be rapid and severe, particularly in young adults who may not realize the risk.
Colchicine and Aminosalicylic Acid
Colchicine, used for gout, has been shown to decrease B12 absorption when taken by mouth. The drug appears to cause reversible damage to the cells lining the lower small intestine, where B12 absorption takes place. Once colchicine is stopped, absorption typically recovers.
Aminosalicylic acid, an older drug still used for tuberculosis treatment, can cause B12 malabsorption through a mechanism that doesn’t involve intrinsic factor. In severe cases, it has caused neurological symptoms consistent with spinal cord damage from B12 deficiency. Both of these medications are used less commonly today, but they remain relevant for people on long-term treatment.
Hormonal Contraceptives
Oral contraceptive pills and injectable hormonal contraceptives do lower measurable B12 levels in blood tests. However, this appears to be misleading. Research following women on hormonal contraception for three years found that very few actually developed truly deficient B12 levels. The current thinking is that these drugs may alter how B12 is distributed or carried in the blood rather than causing a genuine tissue deficiency. Routine B12 testing is not considered necessary for people using hormonal birth control.
Recognizing the Symptoms
Drug-induced B12 deficiency develops gradually, often over months to years, which makes it easy to miss. The earliest signs tend to be vague: fatigue, weakness, lightheadedness, and a general lack of energy. These overlap with so many other conditions that they’re rarely attributed to a vitamin deficiency right away.
Neurological symptoms are more distinctive and more concerning. Tingling or numbness in the hands and feet is a hallmark. Other nerve-related signs include poor balance, difficulty walking, loss of vibration sense, and changes in how you perceive touch. Some people experience cognitive changes: brain fog, memory problems, difficulty concentrating, or personality shifts. Mood disorders, including depression and irritability, are also part of the picture.
Physical signs can include a sore or swollen tongue, pale skin, easy bruising, rapid heartbeat, and unexplained weight loss. Digestive symptoms like diarrhea or constipation sometimes appear as well.
Deficiency Thresholds
A serum B12 level above 300 pg/mL is considered normal. Levels between 200 and 300 pg/mL fall into a borderline zone where additional testing can help clarify whether there’s a functional deficiency. Levels below 200 pg/mL are classified as deficient. If you’re in the borderline range and taking one of the medications listed above, that context makes it more likely the reading reflects a real problem rather than normal variation.
How B12 Deficiency From Medications Is Treated
B12 injections have traditionally been the standard treatment because they bypass the gut entirely, which matters when a medication is blocking normal absorption. However, research shows that high-dose oral B12 supplements (1,000 to 2,000 mcg per day) can be equally effective at restoring normal levels, even in people with absorption problems. This is because at very high doses, a small percentage of B12 is absorbed passively through the intestinal wall, without needing intrinsic factor or the calcium-dependent process that drugs like metformin disrupt.
The choice between injections and high-dose oral supplements often comes down to convenience and preference. For someone with severe neurological symptoms, injections may offer faster correction. For ongoing prevention in someone taking metformin or acid suppressors long-term, a daily high-dose oral supplement is a practical option.