Millions of people take medications called proton pump inhibitors (PPIs) to reduce stomach acid and treat heartburn and ulcers. For years, doctors worried these drugs might cause vitamin B12 deficiency, which can lead to tiredness and nerve problems. Researchers combined results from six studies involving nearly 3,900 people to see if this concern was real. Surprisingly, they found no clear evidence that long-term PPI use actually lowers vitamin B12 levels in the body. However, scientists say more research is needed before we can be completely sure, especially since different studies measured B12 in different ways.

The Quick Take

  • What they studied: Whether taking stomach acid-reducing medications (PPIs) for more than 6 months causes vitamin B12 deficiency
  • Who participated: Nearly 3,900 people from six different research studies—some taking PPIs regularly and some not taking them, across different ages and health conditions
  • Key finding: When researchers looked at blood tests measuring vitamin B12 and a related marker called homocysteine, they found no meaningful difference between people taking PPIs long-term and those not taking them
  • What it means for you: If you take a PPI for heartburn or acid reflux, this research suggests you probably don’t need to worry about automatically developing B12 deficiency from the medication alone. However, this doesn’t mean you should ignore B12 levels entirely—talk to your doctor about your individual risk factors

The Research Details

Researchers searched medical databases for all published studies comparing vitamin B12 levels in people who took PPIs for at least 6 months versus people who didn’t take these drugs. They found six studies that met their strict quality standards. Three of these studies followed groups of people over time (cohort studies), two looked at groups at one point in time (cross-sectional studies), and one was a randomized controlled trial where people were randomly assigned to take PPIs or not.

The researchers then combined the results from all six studies using a special statistical method. This approach allows them to see the overall pattern across many studies rather than relying on just one study. They measured two things in the blood: actual vitamin B12 levels and a substance called homocysteine, which increases when B12 is low.

By combining multiple studies, researchers can see if a pattern holds up across different groups of people and different research methods. This is more reliable than one study alone. However, the studies used different ways to measure B12, which can make it harder to compare results accurately.

The analysis included studies with different designs and methods, which is both a strength and weakness. The strength is that it shows the pattern across different types of research. The weakness is that differences in how studies measured B12 made it harder to get a clear answer. The researchers were transparent about this limitation and called for future studies to use consistent measurement methods.

What the Results Show

The main finding was surprising: when researchers combined all the data, people taking PPIs long-term had virtually the same vitamin B12 levels as people not taking PPIs. The difference was so small it could easily be due to chance. Similarly, homocysteine levels (which rise when B12 is low) showed no meaningful difference between the two groups.

This finding contradicts the common concern that PPIs automatically cause B12 deficiency. The researchers noted that while PPIs do reduce stomach acid, and stomach acid is needed to absorb B12 from food, this doesn’t necessarily translate into actual B12 deficiency in most people.

The results suggest that either the body has enough B12 reserves to handle the reduced absorption, or people eating normal diets get enough B12 despite the medication’s effects. It’s also possible that only certain people are at risk, not everyone taking these drugs.

The researchers noted that the studies they reviewed had some important gaps. Most studies only measured one or two markers of B12 status, but doctors ideally should use multiple markers for accurate diagnosis. Some studies didn’t measure related nutrients like folate and calcium, which also depend on stomach acid for absorption. The studies also didn’t consistently look at different age groups or different doses of PPIs, so we don’t know if certain groups might be at higher risk.

Previous research has been mixed and confusing. Some older studies suggested PPIs might lower B12, while others found no connection. This systematic review helps clarify that the concern may have been overstated. However, it’s important to note that individual case reports of B12 deficiency in PPI users do exist—they’re just not common enough to show up clearly in large population studies.

The biggest limitation is that only six studies met the researchers’ quality standards, and these studies used different methods to measure B12. This makes it harder to combine the results confidently. Additionally, the studies didn’t always measure all the important markers of B12 status—some only checked one marker instead of multiple ones. The studies also didn’t break down results by age, PPI dose, or how long people had been taking the medication, so we can’t say whether certain groups might be at higher risk. Finally, most studies were relatively small, so they might have missed rare cases of B12 deficiency.

The Bottom Line

Based on this research, routine B12 monitoring is probably not necessary for people taking PPIs at standard doses for short to medium periods (moderate confidence). However, if you have risk factors for B12 deficiency—such as being over 65, having digestive disorders, being vegetarian or vegan, or taking PPIs for many years—talk to your doctor about whether B12 monitoring makes sense for you (high confidence). If you experience symptoms like unusual tiredness, tingling in your hands or feet, or memory problems, mention these to your doctor regardless of PPI use.

This research is most relevant to people taking PPIs for heartburn, acid reflux, or ulcers who worry about B12 deficiency. It’s also important for doctors deciding whether to routinely check B12 levels in PPI users. People at higher risk for B12 deficiency (older adults, vegetarians, those with digestive disorders) should still discuss monitoring with their doctor. This research is less relevant to people taking PPIs short-term (less than 6 months) or those already diagnosed with B12 deficiency.

If you’re concerned about B12 deficiency from PPI use, symptoms typically develop slowly over months to years, not weeks. If your doctor recommends checking B12 levels, one test is usually enough unless you have risk factors. If you do need B12 supplementation, you might notice improved energy within a few weeks, though it can take months for nerve-related symptoms to improve.

Want to Apply This Research?

  • If you take a PPI regularly, track your energy levels and any symptoms like tingling, numbness, or unusual fatigue using a simple daily 1-10 scale. Note any changes in your diet (especially if you reduce animal products) or if your doctor recommends B12 testing. This helps you and your doctor identify patterns over time.
  • If you’re concerned about B12 status while taking PPIs, focus on eating B12-rich foods regularly: meat, fish, eggs, dairy products, or fortified plant-based foods. If you’re vegetarian or vegan, consider a B12 supplement or fortified foods. Keep a simple food log noting B12 sources to ensure adequate intake. Discuss with your doctor whether supplementation makes sense for your situation.
  • Set a reminder to discuss B12 status with your doctor at your annual checkup, especially if you’ve been taking PPIs for more than a year or have risk factors for deficiency. If your doctor recommends B12 testing, note the results and any symptoms you experienced. Track whether you notice changes in energy or symptoms after any dietary changes or supplementation recommendations.

This research summary is for educational purposes only and should not replace professional medical advice. While this meta-analysis found no clear association between long-term PPI use and B12 deficiency in the overall population, individual cases of deficiency do occur. If you take PPIs and are concerned about B12 status, or if you experience symptoms like fatigue, numbness, or tingling, consult your healthcare provider. Do not stop taking prescribed medications without medical guidance. Your doctor can assess your individual risk factors and recommend appropriate monitoring or supplementation based on your specific health situation.