What Medications Does Vitamin B12 Interfere With? A Guide to Drug-Induced Deficiencies

October 12, 2025 •

5 min read

A large study published in the Journal of the American Medical Association found that long-term use of common heartburn medications significantly increases the risk of vitamin B12 deficiency. Understanding what medications does vitamin B12 interfere with is essential for patients and healthcare providers to identify risks and prevent potential health complications, such as anemia and nerve damage.

Quick Summary

Chronic use of certain medications, including acid reducers, metformin, and some antibiotics, can impair the body's ability to absorb or utilize vitamin B12, leading to potential deficiency.

Key Points

Common Culprits: Long-term use of gastric acid inhibitors, like omeprazole and famotidine, and the diabetes drug metformin, are major causes of drug-induced vitamin B12 deficiency.
Absorption Interference: Many medications interfere with B12 by impairing the absorption process, either by reducing stomach acid or affecting intestinal function.
Neurological Risk: Inactivation of vitamin B12 by nitrous oxide can cause severe and potentially irreversible neurological damage, especially with pre-existing deficiency.
Delayed Symptoms: Due to the body's B12 storage capacity, deficiency from chronic medication may not appear for years, emphasizing the need for long-term monitoring.
Monitoring is Key: Patients on chronic medication, particularly the elderly or those with digestive issues, should discuss regular vitamin B12 monitoring with their doctor.
Supplementation Options: Management may include high-dose oral supplements or injections, with the best route depending on the specific cause of the malabsorption.
Consult a Professional: Never discontinue a prescribed medication without first speaking to your doctor, who can help manage potential nutrient deficiencies safely.

How Medication Affects Vitamin B12 Absorption

Vitamin B12, or cobalamin, is a vital nutrient necessary for red blood cell formation, neurological function, and DNA synthesis. The body requires sufficient stomach acid and a protein called intrinsic factor to properly absorb vitamin B12 from food. When certain medications disrupt this process, it can lead to a deficiency, especially with long-term use. Unlike other vitamins, B12 is stored in the liver, so a deficiency may take years to become apparent, often emerging only after chronic drug exposure has depleted the body's reserves. This makes awareness and proactive monitoring critical for individuals on long-term drug therapies.

Gastric Acid-Suppressing Medications

Among the most common culprits for drug-induced vitamin B12 deficiency are medications that reduce stomach acid. This class of drugs is widely used to treat gastroesophageal reflux disease (GERD) and peptic ulcers. Stomach acid is required to separate vitamin B12 from the food proteins it's bound to, making it available for absorption. By suppressing this acid, these medications impede the initial step of B12 release.

Proton Pump Inhibitors (PPIs): Drugs like omeprazole (Prilosec), lansoprazole (Prevacid), and esomeprazole (Nexium) are potent acid suppressants. Studies have shown a significant association between long-term PPI use and a higher risk of B12 deficiency. The risk appears to increase with higher doses and longer duration of use, often defined as more than two years.

Histamine-2 Receptor Antagonists (H2 Blockers): Medications such as famotidine (Pepcid AC) and cimetidine (Tagamet) also reduce stomach acid production, though generally less potently than PPIs. Similar to PPIs, prolonged use of H2 blockers has been linked to an increased risk of B12 deficiency by interfering with nutrient absorption.

Metformin

Metformin is a first-line medication for managing type 2 diabetes and is prescribed to millions worldwide. Extensive evidence shows a strong association between long-term metformin therapy and reduced vitamin B12 levels. The primary mechanism is thought to involve interference with calcium-dependent B12 absorption in the small intestine. The risk of developing a deficiency increases with the dose and duration of metformin use, with some research highlighting higher risk after five years or more of treatment. Neuropathy symptoms, which can be mistakenly attributed solely to diabetes, may worsen in patients with concurrent metformin-induced B12 deficiency. Monitoring B12 levels is recommended for patients on long-term metformin, especially those with pre-existing risk factors or symptoms of neuropathy.

Other Medications Causing B12 Interference

Beyond acid reducers and metformin, several other drug classes and agents can impact vitamin B12 status:

Nitrous Oxide: Known as 'laughing gas', nitrous oxide is an anesthetic used in medical procedures and recreationally. It can cause irreversible oxidation of vitamin B12, rendering it inactive. This can cause neurological degeneration, particularly in individuals with pre-existing low B12 levels, sometimes after a single exposure.
Colchicine: This anti-inflammatory medication, used to treat gout, can impair B12 absorption by disrupting the function of ileal mucosal cells.
Chloramphenicol: This antibiotic can interfere with the therapeutic effects of B12 by suppressing bone marrow function, which is critical for red blood cell production.
Anti-seizure Medications: Drugs like phenobarbital and phenytoin can interfere with B12 absorption.
Aminosalicylic Acid (Paser): Used for digestive issues, this medication can lower the body's ability to absorb B12.
Bile Acid Sequestrants: These drugs, such as cholestyramine, bind to bile acids and can also interfere with B12 absorption.
Excessive Vitamin C Intake: Taking large doses of Vitamin C supplements alongside B12 can potentially decrease the amount of B12 available in the body.
Oral Contraceptives: Some studies suggest oral contraceptives can lower B12 levels, although this is often considered to be a 'falsely low' result due to effects on B12 binding proteins, and the clinical significance is debated.

Monitoring and Managing Drug-Induced B12 Deficiency

For those on chronic medication, proactive monitoring is key, especially if risk factors like older age, veganism, or digestive disorders are also present. If a deficiency is suspected, a doctor can order a blood test to check B12 levels. If levels are low, supplementary B12 may be necessary. Options include high-dose oral tablets, sublingual supplements, or intramuscular injections. The best approach depends on the underlying cause and severity of the deficiency. For example, some individuals with absorption issues may require injections to bypass the digestive tract. In some cases, a healthcare provider might consider adjusting the medication dosage or switching to an alternative drug, if clinically appropriate.

Medication Interactions with Vitamin B12: Comparison Table


Drug Class	Common Examples	Mechanism of Interference	Increased Risk Factors
Gastric Acid Inhibitors	Omeprazole (Prilosec), Famotidine (Pepcid)	Reduce stomach acid required to separate B12 from food proteins, impairing absorption.	Long-term use (over 2 years) and high doses.
Metformin	Glumetza, Fortamet	Interferes with the calcium-dependent binding and absorption of B12 in the small intestine.	High dose, prolonged use (over 5 years), existing risk factors for B12 deficiency.
Nitrous Oxide	Laughing Gas (Medical/Recreational)	Irreversibly oxidizes and inactivates vitamin B12, preventing its function.	Long-term or even single-exposure use, especially with pre-existing low B12.
Colchicine	Colcrys, Mitigare	Alters the function of the ileal mucosa, where B12 is absorbed.	Higher doses.
Antibiotics	Chloramphenicol, Aminosalicylic acid	Chloramphenicol affects bone marrow function; Aminosalicylic acid impairs general absorption.	Chronic use or use in patients with anemia.
Anti-seizure Meds	Phenytoin (Dilantin), Phenobarbital	Can interfere with the absorption of B12 in the gut.	Long-term therapy.

Conclusion

While medication is essential for managing a wide range of health conditions, it is crucial to be aware of potential drug-nutrient interactions. Several widely prescribed drugs, from antacids to metformin, can significantly impact the body's vitamin B12 status, particularly with chronic use. Patients on these medications should maintain a dialogue with their healthcare providers about nutritional status and potential side effects. Regular monitoring and, when necessary, appropriate supplementation can effectively prevent or manage deficiencies. If you are concerned about your vitamin B12 levels, do not stop your prescribed medication without consulting your doctor first. A coordinated approach with your healthcare team is the best way to maintain both your health condition and your overall nutritional well-being.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult with a qualified healthcare provider for any health concerns or before making decisions about your treatment.

Frequently Asked Questions

Yes, many people on long-term metformin therapy take B12 supplements. The American Diabetes Association recommends considering a periodic assessment of B12 levels for patients on long-term metformin. If a deficiency is found, supplementation can help prevent or treat neuropathy and other symptoms.

Medications like Proton Pump Inhibitors (PPIs) and H2 blockers reduce stomach acid, which is necessary to free B12 from the proteins in food. Without sufficient acid, the body cannot absorb dietary B12 properly, leading to a deficiency over time.

Yes, other medications include the anesthetic nitrous oxide, the gout medication colchicine, certain antibiotics like chloramphenicol, and some anti-seizure medications such as phenytoin.

It can take several years for a deficiency to develop, as the body stores a significant amount of B12 in the liver. A deficiency typically only becomes apparent after these stores have been depleted due to chronic interference from medication.

The risk of drug-induced B12 deficiency is primarily associated with long-term, chronic use of certain medications, not occasional use. However, if you have other risk factors, like a vegan diet or a digestive disorder, it's wise to be vigilant.

Generally, B12 supplementation does not interfere with the action of the medications mentioned. Instead, it is the medication that interferes with the body's B12 absorption. Taking supplements helps to correct the resulting deficiency.

Symptoms of B12 deficiency include fatigue, weakness, numbness, tingling, and a sore tongue. A blood test can confirm a low B12 level. If you are on long-term medication and experience these symptoms, consult your doctor for testing.