Medications affecting Vitamin B-12 absorption.

PPIs, Metformin, and Vitamin B-12: Are You at Risk for Deficiency?

Soraya Malik in Health & Wellness July 2025 • 4 min read.

"Uncover the surprising link between common medications and Vitamin B-12 deficiency – and what you can do to protect your health."

If you're among the millions who regularly take medications like proton pump inhibitors (PPIs) for heartburn, H2-receptor antagonists (H2RAs), or metformin for diabetes, it's important to be aware of a potential hidden risk: Vitamin B-12 deficiency. While these drugs are effective in treating their respective conditions, research indicates they can also interfere with your body's ability to absorb Vitamin B-12.

Vitamin B-12 is crucial for nerve function, red blood cell production, and DNA synthesis. A deficiency can lead to a range of health issues, from fatigue and weakness to neurological problems. That's why understanding how these common medications might impact your B-12 levels is essential for maintaining your overall well-being.

This article dives into the connection between PPIs, H2RAs, metformin, and Vitamin B-12 deficiency. We'll explore how these drugs can disrupt B-12 absorption, discuss the clinical implications of this deficiency, and provide practical steps you can take to protect your health. Find out what you need to know to stay informed and proactive about your Vitamin B-12 levels.

How Do These Medications Affect Vitamin B-12 Absorption?

Medications affecting Vitamin B-12 absorption.

To understand the potential impact of these medications, it's helpful to know how Vitamin B-12 is normally absorbed. The process is complex, involving several steps:

When you eat foods containing B-12 (primarily from animal sources), the vitamin is bound to proteins. Stomach acid and an enzyme called pepsin are needed to release B-12 from these proteins.

Once freed, B-12 binds to a protein called R-binder (also known as haptocorrin) in the saliva and stomach.
As the B-12/R-binder complex enters the small intestine, pancreatic enzymes release B-12.
B-12 then binds to intrinsic factor (IF), a protein produced by the stomach.
The B-12/IF complex travels to the ileum (the final part of the small intestine), where it's absorbed into the bloodstream. This absorption process relies on calcium.
Finally, in the blood, B-12 binds to transcobalamin, a transport protein that delivers it to cells throughout the body.

PPIs and H2RAs reduce stomach acid production. This can hinder the release of B-12 from food proteins, reducing the amount of B-12 available for absorption. Metformin, commonly used for diabetes, appears to interfere with the calcium-dependent absorption of the B-12/IF complex in the ileum. So, with all of these steps that are need, interfering with even one can cause issues.

Protecting Your Vitamin B-12 Levels: What You Can Do

If you're taking PPIs, H2RAs, or metformin long-term, it's wise to be proactive about monitoring your Vitamin B-12 status. Talk to your doctor about getting your B-12 levels checked, especially if you experience symptoms like fatigue, weakness, or neurological issues.

While some experts believe routine screening isn't necessary for everyone on these medications, assessing your B-12 status before starting the medication and monitoring it periodically is a reasonable approach, especially for those with existing risk factors for deficiency.

Consider talking to your doctor about Vitamin B-12 supplementation. Since PPIs and H2RAs interfere with the absorption of B-12 from food, supplements can help bypass this issue. Oral supplements are safe and readily available. For those taking Metformin, it is important to test calcium levels and replenish calcium, along with consulting on B12 levels. Stay informed, work closely with your healthcare provider, and take proactive steps to maintain healthy Vitamin B-12 levels.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1093/advances/nmy023, Alternate LINK

Title: Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, And Vitamin B-12 Deficiency: Clinical Implications

Subject: Nutrition and Dietetics

Journal: Advances in Nutrition

Publisher: Oxford University Press (OUP)

Authors: Joshua W Miller

Published: 2018-07-01

Everything You Need To Know

How do proton pump inhibitors, H2-receptor antagonists, and metformin affect Vitamin B-12 absorption?

Proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) reduce stomach acid production, which is necessary to release Vitamin B-12 from food proteins. Metformin, a common diabetes medication, interferes with the calcium-dependent absorption of the B-12/intrinsic factor complex in the ileum. By disrupting these processes, these medications can decrease the amount of Vitamin B-12 absorbed by the body. Other medications not mentioned here might also affect absorption through different mechanisms.

Can you explain the normal process of Vitamin B-12 absorption in the body?

Vitamin B-12 absorption is a multi-step process that begins in the stomach, where B-12 is released from food proteins with the help of stomach acid and pepsin, then binds to R-binder. In the small intestine, B-12 is released from R-binder and binds to intrinsic factor (IF). This B-12/IF complex is then absorbed in the ileum with the help of calcium. Finally, in the blood, B-12 binds to transcobalamin for transport throughout the body. Interference at any stage can lead to deficiency.

Why is Vitamin B-12 important, and what are the clinical implications of a deficiency?

Vitamin B-12 is essential for nerve function, red blood cell production, and DNA synthesis. A deficiency can manifest as fatigue, weakness, or neurological problems. Therefore, if you are taking medications that may impair B-12 absorption, it's crucial to monitor your B-12 levels and consult with your healthcare provider, especially if you experience any of these symptoms. Long-term deficiency can lead to irreversible nerve damage, so early detection and management are key.

What steps can I take to protect my Vitamin B-12 levels if I'm taking proton pump inhibitors, H2-receptor antagonists or metformin?

If you are taking proton pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), or metformin long-term, discuss your Vitamin B-12 status with your doctor. Regular monitoring of B-12 levels is recommended, particularly if you experience symptoms like fatigue, weakness, or neurological issues. The strategies to protect Vitamin B-12 levels may include dietary changes, supplements or alternative medications.

Are there other medications or conditions besides proton pump inhibitors, H2-receptor antagonists, and metformin that could also impact Vitamin B-12 levels?

While the focus here is on proton pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), and metformin, other medications that affect stomach acid production or intestinal absorption could also potentially impact Vitamin B-12 levels. Individuals with conditions affecting stomach acid production or intestinal function may also be at higher risk of Vitamin B-12 deficiency, even without taking these specific medications. Further investigation of drug interactions might reveal even more medications of concern.