Understanding: What Drug Depletes B12?

October 6, 2025 •

4 min read

According to the National Institutes of Health, several commonly used medications can interfere with vitamin B12 absorption, making it crucial to understand what drug depletes B12 and its potential health consequences. This guide explores the most common pharmaceutical culprits and the impact they can have on your body's vital nutrient levels.

Quick Summary

Several common drugs, including Metformin, acid-suppressing medications, and nitrous oxide, can cause vitamin B12 depletion by interfering with its absorption or metabolism. Long-term use and higher doses increase the risk, leading to neurological and hematological complications. Monitoring B12 levels and supplementation may be necessary for affected individuals.

Key Points

Metformin: A common diabetes drug, Metformin interferes with the absorption of vitamin B12 in the small intestine, with risk increasing over time and with higher doses.
Acid-Suppressing Drugs (PPIs/H2RAs): Medications like omeprazole (PPI) and famotidine (H2RA) can cause B12 deficiency by reducing the stomach acid needed to release the vitamin from food.
Nitrous Oxide: This substance, used recreationally or medically, inactivates the B12 coenzyme, causing a functional deficiency even when serum levels appear normal.
Symptom Recognition: Common symptoms of B12 deficiency include fatigue, numbness, tingling in extremities, and memory issues, which can mimic other conditions.
Monitoring is Key: Patients on long-term depleting medications should discuss periodic monitoring of their B12 levels with a healthcare provider to catch deficiencies early.
Supplementation Options: Depending on the severity and cause, supplementation can range from high-dose oral tablets to injections to correct the deficiency.

The Crucial Role of Vitamin B12

Vitamin B12, or cobalamin, is an essential water-soluble vitamin vital for numerous bodily functions. It plays a critical role in red blood cell formation, neurological function, and DNA synthesis. The body cannot produce its own B12, so it must be obtained through animal-based foods like meat, dairy, and eggs, or from fortified products. The absorption process is complex, beginning in the stomach where gastric acid releases B12 from food proteins. It then binds to a protein called intrinsic factor before being absorbed in the small intestine. Any interruption in this delicate process, whether due to a medical condition or medication, can lead to deficiency. The human body stores a significant amount of B12 in the liver, which can mask a developing deficiency for years, leading to a delayed diagnosis of related symptoms like fatigue, numbness, or tingling.

The Top Culprits: Common Medications That Deplete B12

Metformin and Its Impact on B12

Metformin is a first-line oral medication for type 2 diabetes and prediabetes, prescribed to millions of people globally. Evidence shows that its long-term use is a known risk factor for reduced vitamin B12 levels, especially with higher doses and longer treatment duration. The mechanism is thought to be multifactorial, but the most accepted theory suggests metformin interferes with calcium-dependent B12 absorption in the small intestine. This can affect the binding of the intrinsic factor-B12 complex to the cubilin receptor in the terminal ileum. Periodic monitoring of B12 levels is recommended for patients taking metformin, particularly those with risk factors like anemia or neuropathy.

The Role of Acid-Suppressing Drugs

Proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) are widely used to treat acid-related disorders like gastroesophageal reflux disease (GERD) and peptic ulcers. These medications work by reducing stomach acid production. However, gastric acid is necessary to release B12 from food, and its suppression can impair this process, leading to malabsorption.

Proton Pump Inhibitors (PPIs): Include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid). Long-term use (typically more than two years) is significantly associated with an increased risk of B12 deficiency.
H2-Receptor Antagonists (H2RAs): Include cimetidine (Tagamet) and famotidine (Pepcid). These have also been linked to B12 malabsorption, though typically with a lower risk compared to PPIs.

Nitrous Oxide: A Unique Pathway of Depletion

Nitrous oxide, often used as an anesthetic in medical and dental procedures and sometimes recreationally, causes a unique form of B12 depletion. It oxidizes the cobalt ion within the vitamin B12 molecule, rendering it inactive. This leads to a functional B12 deficiency, meaning that even if serum B12 levels appear normal, the vitamin cannot be properly utilized by the body. This can lead to severe neurological consequences, including subacute combined degeneration of the spinal cord. Prompt cessation of nitrous oxide exposure and B12 supplementation is necessary for recovery.

Other Medications with B12 Depleting Effects

Beyond the most common culprits, several other drug classes and individual medications have been shown to affect B12 levels:

Antiseizure Medications: Drugs like phenobarbital and phenytoin can interfere with B12 absorption.
Colchicine: Used for gout, colchicine can reduce B12 absorption by affecting receptors in the ileum.
Aminosalicylic Acid: Used for digestive problems, this can lower B12 absorption.
Oral Contraceptives: Some studies suggest a link between oral birth control and lower B12 levels, although results are mixed and more research is needed.

Managing Medication-Induced B12 Deficiency

For individuals on long-term medication known to deplete B12, proactive management is key to preventing complications. Your healthcare provider should monitor your B12 status, especially if you have existing risk factors like older age, gastric surgery, or veganism.

Common management strategies include:

Regular Monitoring: Periodic blood tests to check B12, homocysteine, and methylmalonic acid (MMA) levels are vital. MMA and homocysteine are more sensitive indicators of tissue-level deficiency.
Supplementation: Oral B12 supplements are often effective, as high doses can overcome malabsorption issues. In cases of severe deficiency or impaired absorption, intramuscular injections may be required.
Dosage or Medication Changes: In consultation with a doctor, adjusting the medication dosage or considering alternative treatments may be appropriate.
Addressing the Cause: The underlying cause of the B12 deficiency must be treated. For instance, in cases of nitrous oxide abuse, cessation of use is paramount.

Comparison of B12-Depleting Medications


Medication Class	Examples	Primary Mechanism of Depletion	Typical Onset/Risk Factors
Metformin	Glumetza, Fortamet	Interferes with calcium-dependent B12 absorption in the ileum.	Long-term and high-dose use increase risk. Diabetes, peripheral neuropathy are key indicators.
Proton Pump Inhibitors (PPIs)	Omeprazole (Prilosec), Lansoprazole (Prevacid)	Suppresses gastric acid, which is needed to cleave B12 from food proteins.	Chronic use (often >2 years) and higher doses are associated with greater risk.
H2-Receptor Antagonists (H2RAs)	Cimetidine (Tagamet), Famotidine (Pepcid)	Also suppresses gastric acid, though generally less potent than PPIs.	Similar to PPIs, but lower risk. Long-term use is a factor.
Nitrous Oxide	Laughing Gas	Oxidizes and inactivates the cobalt center of the B12 molecule, leading to functional deficiency.	Recreational abuse, even in short durations, or exposure in susceptible individuals.
Colchicine	Colcrys, Mitigare	Inhibits B12 absorption by reducing intrinsic factor receptor levels in the ileum.	Use to prevent or treat gout attacks.

Conclusion

Medication-induced vitamin B12 deficiency is a significant and often overlooked side effect that can have serious health consequences, particularly neurological and hematological issues. Recognizing what drug depletes B12 is the first step toward effective management. For patients on long-term treatment with medications like metformin, PPIs, H2RAs, or those with recreational nitrous oxide exposure, awareness and regular monitoring of B12 status are crucial. With the proper guidance from a healthcare professional, this condition can be effectively treated with supplementation, preventing long-term damage and improving overall health. Discussing your medication list with your doctor can ensure any potential nutrient deficiencies are identified and addressed proactively.

Additional Resources

For more information on vitamin B12 and its health implications, visit the National Institutes of Health Office of Dietary Supplements.

Frequently Asked Questions

Metformin primarily interferes with the absorption of vitamin B12 in the small intestine by affecting the calcium-dependent pathway necessary for B12 to bind to its intestinal receptor.

PPIs and H2-receptor antagonists reduce the production of gastric acid. This acid is required to separate vitamin B12 from the food protein it's bound to, leading to impaired absorption over time.

Yes, chronic or heavy recreational use of nitrous oxide can deplete B12. It uniquely inactivates the vitamin B12 molecule, leading to a functional deficiency and potentially severe neurological damage.

Because the body has large B12 stores in the liver, it can take several years of consistent medication use, especially with PPIs or metformin, before a deficiency develops and becomes clinically evident.

Yes, B12 deficiency caused by medication can often be reversed with supplementation (oral tablets or injections) and, when appropriate, addressing the underlying cause. However, nerve damage from long-term deficiency may not always be fully reversible.

Yes, older adults are often at higher risk because they may already have lower baseline B12 levels and common co-morbidities. Their absorption is often less efficient, and they may be on long-term medications that further impact B12 status.

No, you should never stop or change your medication without consulting a healthcare professional. A doctor can help determine if there is a deficiency and create a management plan that might include supplementation, allowing you to continue your necessary treatment.