Vitamin B12 deficiency has a surprisingly long list of causes, ranging from what you eat to medications you may already be taking. The common thread is that B12 has one of the most complex absorption pathways of any vitamin, and a problem at any step can leave you short. Understanding which cause applies to you matters because the fix is different for each one.
How B12 Absorption Works (and Where It Breaks Down)
B12 absorption depends on a chain of events that starts in your stomach and ends in the last section of your small intestine. Cells in your stomach lining produce a protein called intrinsic factor, which binds to B12 from food. That B12-intrinsic factor pair then travels to the end of the small intestine, where it’s absorbed into the bloodstream. If your stomach doesn’t make enough intrinsic factor, your small intestine is damaged, or you simply aren’t eating enough B12, the chain breaks.
Diet: The Most Straightforward Cause
B12 is found almost exclusively in animal products: meat, fish, eggs, and dairy. If you eat little or none of these foods, deficiency is likely without supplementation. Studies show that roughly 52% of vegans have deficient B12 levels, compared to about 1% of people eating a mixed diet. One European study found even higher rates, with 92% of vegans and 77% of lacto-ovo vegetarians falling below the deficiency threshold.
These numbers reflect people who aren’t supplementing. With consistent B12 supplements or fortified foods, vegans and vegetarians can maintain normal levels. But the margin for error is thin: your body stores enough B12 to last a few years, so deficiency from a dietary shift can take time to show up, often catching people off guard well after they’ve changed their eating habits.
Pernicious Anemia: When Your Immune System Is the Problem
Pernicious anemia is an autoimmune condition in which your immune system attacks either the intrinsic factor protein itself or the stomach cells that produce it. Without intrinsic factor, you can eat plenty of B12-rich foods and still become severely deficient because the vitamin passes through your gut without being absorbed. This is the classic cause of B12 deficiency and tends to develop gradually, most often in adults over 60. It requires lifelong B12 replacement, typically through injections that bypass the gut entirely.
Medications That Quietly Deplete B12
Two of the most widely prescribed drug classes can lower your B12 levels over time.
Proton Pump Inhibitors (PPIs)
Acid-suppressing medications used for heartburn and reflux reduce the stomach acid needed to release B12 from food. Taking PPIs for two or more years raises the risk of B12 deficiency by about 65% compared to non-users. The longer you take them, the greater the concern. If you’ve been on a PPI for years and haven’t had your B12 checked, it’s worth asking about.
Metformin
The most common medication for type 2 diabetes interferes with B12 absorption in the small intestine. About 7.5% of metformin users develop confirmed B12 deficiency. Routine B12 screening isn’t currently standard for everyone on metformin, but experts recommend it for people with additional risk factors like older age, a vegetarian diet, or concurrent PPI use.
Stomach and Gut Conditions
Any condition that damages the stomach lining or the lower small intestine can impair B12 absorption. Celiac disease is a significant contributor: studies find B12 deficiency in 12% to 41% of people with celiac disease, depending on how active the disease is and whether it’s being managed with a gluten-free diet. Rates tend to drop substantially once the intestinal lining heals.
Crohn’s disease poses a particular risk when it affects the terminal ileum, the specific stretch of intestine where B12 is absorbed. Surgical removal of that section, which sometimes becomes necessary, permanently eliminates the body’s ability to absorb B12 from food.
Helicobacter pylori infection, the bacterium responsible for most stomach ulcers, can also contribute. Chronic H. pylori infection causes inflammation and thinning of the stomach lining, which impairs both acid production and intrinsic factor secretion. Treating the infection can help restore normal absorption.
Weight Loss Surgery
Bariatric surgery is one of the most predictable causes of B12 deficiency. Procedures like Roux-en-Y gastric bypass reroute food past the stomach and upper intestine, drastically reducing the area available for B12 absorption. B12 deficiency is one of the most common nutrient deficiencies in this population, and most patients need lifelong supplementation, often through injections. Restrictive procedures like sleeve gastrectomy carry a lower risk and can sometimes be managed with oral supplements, but monitoring is still essential.
Nitrous Oxide: A Less Obvious Culprit
Nitrous oxide, commonly known as laughing gas, destroys B12 in a way that’s chemically distinct from every other cause on this list. Rather than blocking absorption, nitrous oxide directly inactivates B12 already in your body by oxidizing the cobalt atom at its core. This makes the vitamin permanently nonfunctional.
Recreational use of nitrous oxide (inhaling from pressurized canisters) can cause severe neurological damage, including numbness and tingling in the hands and feet, muscle weakness, difficulty walking, and even vision problems from optic nerve damage. What makes this especially dangerous is that standard blood tests may show normal B12 levels even while the vitamin is completely inactive. People with an undiagnosed, borderline B12 deficiency are at highest risk, but heavy recreational use can cause damage even in people who previously had adequate levels.
Age-Related Decline
As you get older, your stomach naturally produces less acid and less intrinsic factor. This gradual decline means that even with a diet rich in animal products, your body absorbs less B12 from food over time. Deficiency becomes increasingly common after age 60, which is why many guidelines recommend that older adults get their B12 from supplements or fortified foods rather than relying solely on dietary sources. The crystalline form of B12 used in supplements doesn’t require stomach acid to be absorbed, making it more reliable for aging digestive systems.
How Deficiency Is Confirmed
A standard blood test measures serum B12 levels. Most laboratories define deficiency as levels below 200 to 250 pg/mL, but there’s a gray zone: levels between 150 and 399 pg/mL can be ambiguous. In that range, a follow-up test measuring methylmalonic acid (MMA) can clarify whether your cells are actually short on B12. Normal MMA levels fall below 0.40 µmol/L. When MMA is elevated, it confirms that your body isn’t getting enough usable B12, even if your serum level looks borderline acceptable.
This distinction matters because some causes of deficiency, particularly nitrous oxide exposure, can produce severe symptoms while serum B12 appears normal. If symptoms like persistent tingling, numbness, fatigue, or difficulty with balance don’t match the blood test, MMA testing provides a more accurate picture of what’s happening at the cellular level.