What Medications Deplete B12 Levels? A Pharmacological Review

October 12, 2025 •

4 min read

In the United States and the United Kingdom, the prevalence of vitamin B12 deficiency is approximately 6% in people younger than 60 and nearly 20% in those older than 60. Chronic use of certain drugs raises this risk, begging the question: what medications deplete B12 levels?

Quick Summary

Certain common medications can significantly lower vitamin B12 levels. This includes metformin for diabetes, and acid-reducing drugs like proton pump inhibitors (PPIs) and H2 blockers, by interfering with B12 absorption.

Key Points

Metformin: A common diabetes medication, it can cause B12 deficiency by interfering with its absorption in the small intestine, with risk increasing with dose and duration.
Proton Pump Inhibitors (PPIs): Drugs like omeprazole reduce stomach acid, which is essential for releasing B12 from food, leading to malabsorption with long-term use.
H2 Blockers: Medications such as famotidine also lower stomach acid and are linked to an increased risk of B12 deficiency with chronic use.
Symptoms: Deficiency can manifest as fatigue, tingling in hands and feet, memory problems, a sore tongue, and difficulty walking.
Management: If deficiency is confirmed, treatment often involves B12 supplementation through injections or high-dose oral tablets, which can often be done without stopping the necessary medication.
Risk Factors: The risk of drug-induced B12 deficiency is higher with long-term use, higher dosages, and in older adults.
Awareness is Key: Patients on long-term treatment with metformin, PPIs, or H2 blockers should be aware of the risk and discuss periodic monitoring with their healthcare provider.

The Unseen Link: Drug-Induced Vitamin B12 Deficiency

Vitamin B12, or cobalamin, is a crucial nutrient that supports nerve function, red blood cell formation, and DNA synthesis. While deficiency is often linked to diet or age, a significant and often overlooked cause is the long-term use of several widely prescribed medications. This phenomenon, known as drug-induced nutrient depletion, occurs when a medication interferes with the body's ability to absorb, metabolize, or utilize essential vitamins and minerals. Understanding which drugs are culprits is the first step toward prevention and management.

Key Medications That Interfere with B12 Absorption

Several classes of drugs are well-documented to reduce vitamin B12 levels, primarily by altering the gastrointestinal environment or interfering with the complex absorption process. The risk often increases with the duration and dosage of the medication.

Metformin: The Diabetes Drug Dilemma

Metformin, a first-line treatment for type 2 diabetes used by millions globally, is a known cause of B12 deficiency. Studies indicate that long-term use is linked to lower B12 levels, with the risk rising with higher doses and longer treatment. The prevalence of B12 deficiency in metformin users varies widely, from 6% to 50%.

Mechanism of Depletion: Metformin is thought to interfere with the absorption of the B12-intrinsic factor complex in the small intestine, a process that relies on calcium. It may also impact gut motility and bacteria, further hindering absorption.

Acid-Suppressing Medications: A Double-Edged Sword

Medications that reduce stomach acid are widely used for conditions like GERD and peptic ulcers. However, this reduction in acid negatively impacts B12 absorption.

Proton Pump Inhibitors (PPIs)

Common PPIs include omeprazole, esomeprazole, and lansoprazole. Stomach acid is vital for releasing B12 from food proteins before it can be absorbed. By significantly reducing acid, PPIs hinder this initial step. Extended use (two years or more) is strongly linked to an increased risk of B12 deficiency, with higher doses posing a greater risk.

Histamine H2-Receptor Antagonists (H2 Blockers)

H2 blockers such as famotidine and cimetidine also lower stomach acid, though less effectively than PPIs. Similar to PPIs, they can impede the release of B12 from food, leading to malabsorption over time. Research has shown that prolonged use of H2 blockers is associated with a higher risk of developing B12 deficiency.

Other Implicated Medications

Besides metformin and acid suppressors, other drugs can affect B12 levels:

Colchicine: Used for gout, it can disrupt B12 absorption.
Antiseizure Medications: Some older drugs like phenobarbital may lower B12 absorption.
Chloramphenicol: This antibiotic can interfere with B12's role in red blood cell production.
Aminosalicylic acid: A medication for digestive issues that can reduce B12 absorption.

Comparison of B12 Depleting Medications


Medication Class	Common Examples	Primary Mechanism of B12 Depletion	Risk Factors
Biguanides	Metformin	Interferes with calcium-dependent absorption of the B12-Intrinsic Factor complex in the ileum.	High dose, long duration (>4 years).
Proton Pump Inhibitors (PPIs)	Omeprazole, Esomeprazole	Reduces gastric acid, preventing B12 from being cleaved from food protein.	Long duration (>2 years), high dosage.
H2-Receptor Antagonists	Famotidine, Cimetidine	Reduces gastric acid, interfering with the release of B12 from food.	Chronic use (≥12 months).
Anti-gout Agents	Colchicine	Inhibits B12 absorption by reducing intrinsic factor receptor levels in the ileum.	Chronic use.

Recognizing and Managing Drug-Induced B12 Deficiency

Symptoms of B12 deficiency are often subtle and can worsen gradually, affecting physical, neurological, and psychological health.

Common Symptoms:

Fatigue and weakness
Numbness or tingling in the extremities
Sore, red tongue and mouth sores
Difficulty with balance and walking
Memory issues or confusion
Mood changes like depression
Pale or yellowish skin

If drug-induced B12 deficiency is suspected, a healthcare provider should confirm it with blood tests. Treatment typically involves B12 supplementation, either through injections or high-dose oral tablets. Since supplemental B12 is not bound to protein, acid-suppressing drugs have less impact on its absorption. For those on metformin, supplementation is often enough, and the medication is usually continued due to its importance for glycemic control. Patients on acid suppressors may benefit from using the lowest effective dose for the shortest necessary time.

Conclusion: A Call for Awareness

Several commonly used medications can significantly hinder vitamin B12 absorption, potentially leading to a deficiency with serious health consequences if not addressed. Metformin, PPIs, and H2 blockers are key examples. Individuals on long-term therapy with these drugs, particularly older adults, should be aware of the risk of B12 depletion. Regular monitoring and discussion with healthcare providers about potential symptoms are crucial for early detection and management, ensuring the benefits of these essential medications are maintained without compromising nutritional health.

For more detailed clinical guidelines, you can refer to resources from health authorities such as the UK's National Health Service (NHS).

Frequently Asked Questions

Metformin, a first-line treatment for type 2 diabetes, is one of the most common medications known to decrease vitamin B12 levels, especially with long-term use and at higher doses.

Acid reflux medications like omeprazole (a PPI) and famotidine (an H2 blocker) reduce stomach acid. Gastric acid is required to separate vitamin B12 from the protein in food, so by lowering acid levels, these drugs inhibit B12 absorption.

In some cases, the risk of B12 deficiency decreases after discontinuing the medication, such as with PPIs. However, management typically involves B12 supplementation, and the underlying medication is often continued if it remains necessary for the patient's health.

Early symptoms can be subtle but often include feeling very tired or weak, a sore tongue, numbness or tingling in the hands and feet, and problems with memory or confusion.

The American Diabetes Association recommends periodic measurement of B12 levels in patients taking metformin, especially if they have anemia or peripheral neuropathy. You should consult your healthcare provider to determine if supplementation is necessary for you.

Treatment usually involves replenishing B12 levels with supplements. This can be done with high-dose oral vitamin B12 or through intramuscular injections, especially if neurological symptoms are present.

Yes, the risk of low B12 levels increases with a higher metformin dose and longer treatment duration. Doses of 1500 mg/day or more have been shown to be a major factor related to B12 deficiency.