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Common Causes of Vitamin B12 Deficiency.

by Mansi Dudhat 26 Jun 2026
Common Causes of Vitamin B12 Deficiency.

Vitamin B12 deficiency is one of the most common and most overlooked nutritional problems in the world — yet many people don't find out they have it until real damage has already begun.

The challenge is that symptoms build slowly. Fatigue, brain fog, tingling in the hands and feet, and mood changes can have dozens of causes. By the time a deficiency shows up clearly on a blood test, it may have been developing for months or even years.

Research published in Frontiers in Nutrition in 2025 found deficiency rates ranging from 6 to 15% in adults and children across national and regional surveys, with higher rates in populations with food insecurity, limited animal protein intake, or poor access to fortified foods. The American Academy of Family Physicians reports that roughly 2 to 3% of adults in the United States are deficient, but given how often the condition goes undiagnosed, the real number is likely higher.

Understanding what causes vitamin B12 deficiency is the first step toward protecting your health. There is no single cause. Instead, deficiency typically develops through one of three routes: not eating enough B12, not absorbing it properly, or losing it through medication use or surgery.

How the Body Absorbs Vitamin B12


Before exploring the causes, it helps to understand how B12 absorption normally works — because most causes of deficiency involve a breakdown in this process.

Vitamin B12 (also called cobalamin) is found almost exclusively in animal-based foods: meat, fish, eggs, and dairy. When you eat these foods, stomach acid separates B12 from food proteins. The vitamin then binds to a protein called intrinsic factor, which is produced by parietal cells in the stomach lining. This B12-intrinsic factor complex travels through the digestive tract and is absorbed in the terminal ileum — the final portion of the small intestine.

If anything disrupts this chain — the stomach acid, the parietal cells, the intrinsic factor, or the terminal ileum — absorption fails, regardless of how much B12 you consume.

1. Dietary Causes: Not Eating Enough B12-Rich Foods


The simplest cause of B12 deficiency is dietary: not consuming foods that contain it.

Vegan and Vegetarian Diets


Because B12 is found almost entirely in animal products — red meat, poultry, fish, shellfish, eggs, and dairy — people who avoid these foods have a significantly elevated risk of deficiency. Vegans who do not supplement or eat B12-fortified foods are particularly vulnerable.

This is not a fringe concern. Strict vegetarians and vegans are consistently identified as a high-risk population for B12 deficiency in clinical guidelines, including those from the American Academy of Family Physicians.


Key point:

Plant-based sources of B12 are largely unreliable. Fermented foods, spirulina, and some algae are sometimes cited, but the evidence for their B12 bioavailability is weak. Supplementation or fortified foods are essential for vegans and many vegetarians.


Restrictive Eating Patterns


Poverty, food insecurity, extreme calorie restriction, and eating disorders can all reduce dietary B12 intake to inadequate levels — even in people who are not vegan. Older adults who eat less overall are at heightened risk for this reason.

2. Malabsorption: When the Gut Cannot Absorb B12


Malabsorption is actually the most common overall cause of B12 deficiency in developed countries. You may eat plenty of B12-rich foods and still be deficient if your gastrointestinal system cannot process or absorb the vitamin.


Pernicious Anemia


Pernicious anemia is an autoimmune condition in which the body produces antibodies that attack gastric parietal cells or intrinsic factor itself. When parietal cells are destroyed, intrinsic factor production drops — and without intrinsic factor, B12 cannot be absorbed from food, no matter how much is consumed.

Pernicious anemia is considered one of the leading causes of B12 deficiency in developed countries. It often develops insidiously, progressing for years without a clear diagnosis. Untreated, it can lead to irreversible neurological damage, including a condition called subacute combined degeneration — a demyelination of the spinal cord's dorsal and lateral columns that causes weakness, sensory loss, and difficulty walking.

Because oral B12 supplements are absorbed via a different (passive) pathway in very small amounts, people with pernicious anemia typically need B12 injections rather than tablets to bypass the intrinsic factor problem.


Atrophic Gastritis and Helicobacter pylori Infection


Atrophic gastritis is a chronic inflammation of the stomach lining that progressively destroys acid-producing cells — reducing both stomach acid and intrinsic factor. This impairs the release of B12 from food proteins, a condition known as food-bound cobalamin malabsorption.

According to research published in a peer-reviewed gastroenterology journal, food-bound cobalamin malabsorption is actually the most common cause of B12 deficiency overall. H. pylori infection — one of the world's most prevalent bacterial infections — is a frequent underlying driver of atrophic gastritis.

Atrophic gastritis is particularly common in older adults, which helps explain why age is an independent risk factor for B12 deficiency.


Gastrointestinal Surgery


Gastric bypass surgery, gastrectomy (full or partial removal of the stomach), and surgical removal of the terminal ileum can dramatically impair B12 absorption:

  • Gastric bypass reduces stomach acid and parietal cell function, limiting the release of B12 from food

  • Gastrectomy eliminates or reduces the source of intrinsic factor

  • Ileal resection removes the site where B12 is absorbed


Bariatric surgery patients are routinely advised to take B12 supplements for life — but adherence is inconsistent, and B12 deficiency remains a recognized complication in this population. Research has documented cases where hemoglobin dropped precipitously in gastric bypass patients who stopped taking their supplements.


Inflammatory Bowel Disease: Crohn's Disease and Celiac Disease


Crohn's disease 

frequently affects the terminal ileum — the exact section of bowel responsible for B12 absorption. Active inflammation, scarring, or surgical removal of this segment can make adequate absorption impossible.


Celiac disease

when undiagnosed or poorly managed, damages the intestinal lining broadly, reducing the absorption of multiple nutrients including B12.

Both conditions are identified as independent risk factors for B12 deficiency in clinical screening guidelines.


Pancreatic Insufficiency


The pancreas contributes to B12 absorption by secreting enzymes that help free B12 from its binding proteins. In pancreatic insufficiency — a common complication of chronic pancreatitis or cystic fibrosis — this step is impaired, reducing the amount of B12 available for absorption.

3. Medications That Deplete Vitamin B12


Several widely prescribed medications are associated with reduced B12 absorption. This is one of the most underrecognized causes of deficiency, particularly because patients may take these drugs for years before a deficiency becomes clinically apparent.


Metformin


Metformin is one of the most commonly prescribed medications in the world for type 2 diabetes. Its mechanism of action is well-documented, but its effect on B12 levels is frequently overlooked in routine care.

Long-term metformin use is associated with reduced vitamin B12 absorption, likely by interfering with the calcium-dependent binding of the intrinsic factor–B12 complex to receptors in the terminal ileum. Clinical guidelines from the American Academy of Family Physicians recommend considering B12 screening in patients who have been taking metformin for more than four months.

Studies have found B12 deficiency rates of 20 to 36% or more among diabetic patients on long-term metformin therapy — a significant proportion of a very large patient population.


Proton Pump Inhibitors (PPIs) and H2 Blockers


Proton pump inhibitors such as omeprazole, lansoprazole, and esomeprazole are among the most widely used medications worldwide. H2 blockers (like famotidine and ranitidine) work similarly. Both classes reduce stomach acid production.

Since stomach acid is required to cleave B12 from food proteins in the first step of absorption, long-term use of these medications can progressively deplete B12 levels. The American Academy of Family Physicians advises B12 testing in patients who have used PPIs or H2 blockers for more than 12 months.


Nitrous Oxide


Nitrous oxide (laughing gas) is commonly used in dental procedures and as an anesthetic. It inactivates vitamin B12 by oxidizing its cobalt center, rendering the vitamin non-functional.

Occasional use is unlikely to cause problems in healthy people with normal B12 stores. However, in people with already borderline or low B12 levels, exposure to nitrous oxide can precipitate acute, severe deficiency — including neurological symptoms. This is a concern in both medical settings and in recreational misuse.

4. Age-Related B12 Deficiency


Age is an independent risk factor for B12 deficiency, and the relationship is well-documented across multiple studies.

As people age, stomach acid production declines naturally — a condition called hypochlorhydria or achlorhydria. This reduces the ability to release B12 from food proteins, even in people eating a nutritious diet. Atrophic gastritis, which further reduces acid and intrinsic factor, becomes more prevalent with age.

Research published in the FASEB Journal in 2025, examining 427 individuals, found that adults and the elderly had the highest deficiency rates (41.4% and 42.6%, respectively), while children showed the lowest rates. Mean serum B12 concentrations decreased significantly with age across the study population.

For these reasons, clinical guidelines identify adults over 75 as a high-priority group for B12 screening.

5. Risk Factor Summary

Risk Factor

Mechanism

Estimated Risk Level

Vegan/strict vegetarian diet

Insufficient dietary intake

High

Pernicious anemia

Autoimmune destruction of intrinsic factor

High

Atrophic gastritis

Reduced acid and intrinsic factor production

High

Gastric bypass surgery

Reduced parietal cell function; reduced acid

High

Ileal resection

Removal of the B12 absorption site

High

Crohn's disease (ileal involvement)

Inflammation of absorption site

Moderate–High

Long-term metformin use (>4 months)

Impaired receptor-mediated absorption

Moderate

Long-term PPI/H2 blocker use (>12 months)

Reduced stomach acid; impaired B12 release from food

Moderate

Advanced age (>75 years)

Hypochlorhydria; atrophic changes

Moderate

Celiac disease (unmanaged)

Broad intestinal malabsorption

Moderate

Nitrous oxide exposure

Inactivation of B12

Situational

Pancreatic insufficiency

Impaired B12 release from binding proteins

Moderate



Frequently Asked Questions


What is the most common cause of vitamin B12 deficiency? 


In developed countries, the most common overall cause is food-bound cobalamin malabsorption — a condition where the stomach cannot properly release B12 from food proteins due to reduced acid or intrinsic factor. Atrophic gastritis, pernicious anemia, and certain medications are leading contributors. In developing regions or among plant-based eaters, dietary insufficiency is a primary cause.


Can medications cause vitamin B12 deficiency? 


Yes. Metformin and proton pump inhibitors (PPIs) are the most clinically significant examples. Both are prescribed for long-term use, and both have well-documented associations with declining B12 levels over time. Anyone taking these medications for more than a few months should discuss B12 monitoring with their doctor.


Does a vegan diet always cause B12 deficiency? 


Not necessarily — but without supplementation or regular consumption of B12-fortified foods, the risk is very high. Unlike many other nutrients, B12 has no reliable plant-based food sources. Vegans should supplement consistently and monitor their levels periodically.


Can you be B12 deficient with normal blood tests? 


Serum B12 levels can sometimes appear normal even when a functional deficiency exists. Elevated methylmalonic acid (MMA) and homocysteine are more sensitive markers of early B12 deficiency and are recommended when borderline serum levels are found (180–350 pg/mL).


What happens if B12 deficiency goes untreated?


 Untreated B12 deficiency can cause irreversible neurological damage, including peripheral neuropathy (tingling, numbness), cognitive decline, and in severe cases, subacute combined degeneration of the spinal cord. Megaloblastic anemia and psychological symptoms, including depression, can also develop. The neurological damage, unlike the anemia, may not fully reverse even with treatment.


How is vitamin B12 deficiency diagnosed?


 Initial testing typically includes a complete blood count and serum B12 level. A level below 180 pg/mL is generally diagnostic for deficiency. Borderline levels (180–350 pg/mL) warrant methylmalonic acid testing. Patients without an obvious cause may also be tested for anti-intrinsic factor antibodies and anti-parietal cell antibodies to rule out pernicious anemia.


Who is most at risk for B12 deficiency?


 High-risk groups include vegans and strict vegetarians, people over 75, patients with pernicious anemia, individuals with Crohn's disease or celiac disease affecting the ileum, those who have had gastric surgery, and long-term users of metformin or proton pump inhibitors.

Conclusion


Vitamin B12 deficiency doesn't usually announce itself dramatically. It tends to accumulate quietly — through a diet low in animal products, a stomach that's slowly losing its absorptive capacity, or a medication taken daily without any thought of its effect on nutrient levels.

The good news is that deficiency is treatable, and in most cases preventable, once you understand your personal risk factors. If you fall into one or more of the high-risk categories described in this article — whether you're a long-term vegan, taking metformin or PPIs, over 75, or living with an inflammatory bowel condition — it's worth discussing B12 screening with your doctor.

Early detection matters. The neurological damage that severe, prolonged B12 deficiency can cause may be permanent. Catching a deficiency while it's still mild means a straightforward fix — supplementation, dietary adjustment, or B12 injections if absorption is the issue.

 

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