The Underlying Cause of B12 Deficiency: Understanding the Mechanisms

December 17, 2025 •

4 min read

The vast majority of vitamin B12 deficiency cases are not due to a lack of dietary intake, but rather a problem with absorption. While B12 is abundant in animal products, the complex process required for the body to utilize it means the underlying cause of B12 deficiency is often rooted in digestive issues. This makes identifying the root problem critical for effective treatment and management.

Quick Summary

This article explores the primary drivers of B12 deficiency, including autoimmune conditions like pernicious anemia, surgical procedures affecting the gut, and dietary restrictions. It details the steps of vitamin absorption and explains how issues like intrinsic factor deficiency disrupt this crucial process.

Key Points

Intrinsic Factor is Key: The most common underlying cause of B12 deficiency is an inability to properly absorb the vitamin, often due to a lack of intrinsic factor protein needed for uptake.
Pernicious Anemia is a Major Factor: This autoimmune disease is a leading cause of B12 deficiency because it attacks the stomach cells responsible for producing intrinsic factor.
Surgery Disrupts Absorption: Procedures like gastric bypass or partial stomach removal can eliminate the source of intrinsic factor, causing permanent B12 malabsorption.
Certain Diets Pose a Risk: A strict vegan or vegetarian diet lacking fortified foods or supplements is a direct cause, as B12 is found primarily in animal products.
Medications and Age Affect Absorption: Long-term use of certain drugs, including metformin and acid reflux medications, and the aging process itself, can decrease B12 absorption.
Intestinal Issues Interfere with Uptake: Chronic conditions like Crohn's and celiac disease can damage the ileum, preventing the absorption of the B12-intrinsic factor complex.
Parasites Steal B12: Rare infections from parasites like the fish tapeworm can consume B12, leading to a deficiency in the host.

The B12 Absorption Process: A Complex Journey

To understand what can go wrong, one must first grasp the normal process of vitamin B12 absorption. Unlike many other vitamins, B12 requires several steps and specific proteins to be absorbed effectively.

Release from Food: In the stomach, hydrochloric acid and enzymes separate vitamin B12 from the food proteins it's bound to.
Binding with Intrinsic Factor: The now-free B12 then combines with a special glycoprotein called intrinsic factor (IF), which is produced by the parietal cells in the stomach.
Transport and Absorption: This B12-IF complex travels to the final section of the small intestine (the ileum), where it binds to receptors and is absorbed into the bloodstream.
Circulation: Once absorbed, B12 is carried through the blood by a transport protein, transcobalamin II, to various tissues and the liver for storage.

Problems can occur at any stage of this journey, but issues with intrinsic factor production and absorption in the small intestine are the most frequent culprits.

Leading Causes of B12 Malabsorption

Pernicious Anemia

Pernicious anemia is an autoimmune disease and the most common cause of B12 deficiency globally. In this condition, the immune system mistakenly attacks the parietal cells of the stomach that produce intrinsic factor, leading to a severe shortage. Without enough intrinsic factor, the B12-IF complex cannot form, and the vitamin cannot be absorbed, regardless of how much is consumed.

Gastrointestinal Surgery

Surgical procedures that remove parts of the stomach or the small intestine are a common cause of B12 deficiency. Gastric bypass surgery, for instance, often results in the partial or complete loss of the parietal cells that produce intrinsic factor, while the removal of the ileum (due to conditions like Crohn's disease) can remove the site where the B12-IF complex is absorbed. For these patients, lifelong B12 supplementation is often necessary.

Chronic Digestive Disorders

Several chronic conditions can disrupt B12 absorption. Celiac disease, if untreated, and Crohn's disease can both cause inflammation and damage to the lining of the small intestine, impairing its ability to absorb the vitamin. Small Intestine Bacterial Overgrowth (SIBO) is another condition where an excess of bacteria in the small intestine competes with the body for available B12.

Medications and Other Factors

Certain medications can interfere with B12 absorption, particularly if used long-term. This includes metformin for diabetes, as well as proton pump inhibitors (PPIs) and H2 receptor antagonists for heartburn, which reduce the stomach acid needed to release B12 from food. Additionally, chronic excessive alcohol consumption can damage the stomach lining and intestinal tract, leading to poor absorption.

Dietary Insufficiency as a Cause

While absorption problems are most common, inadequate dietary intake is a clear underlying cause for certain populations. Since vitamin B12 is produced by bacteria and primarily found in animal products, strict vegans and vegetarians are at a significant risk for deficiency if they do not supplement. The body stores large amounts of B12, so it can take several years for a deficiency to manifest, but it is a serious and preventable issue. Breastfed infants of vegan mothers are also at risk.

Malabsorption vs. Dietary Deficiency: A Comparison


Feature	Malabsorption (e.g., Pernicious Anemia)	Dietary Deficiency (e.g., Veganism)
Primary Cause	Impaired ability to absorb B12 due to intrinsic factor deficiency or intestinal damage.	Insufficient intake of B12 from food sources.
Mechanism	Intrinsic factor is missing, or the site of absorption is damaged.	No animal products are consumed, which are the main source of B12.
Affected Population	People over 50, those with autoimmune diseases, or post-GI surgery.	Strict vegans and vegetarians, and their breastfed infants.
Symptom Onset	Often slow and insidious; can take years due to liver reserves.	Can also take years depending on initial body stores and supplement use.
Treatment	Injections or high-dose oral supplements, often for life, to bypass the absorption issue.	Oral supplements or fortified foods are usually effective.

The Role of Other Digestive Factors

Gastritis and Low Stomach Acid

Atrophic gastritis, an inflammation of the stomach lining, is a significant cause of B12 deficiency, particularly in older adults. This condition reduces the stomach's production of hydrochloric acid, which is necessary to free B12 from food proteins, and can also lead to a lack of intrinsic factor. This issue is why older individuals often absorb B12 more easily from supplements than from food.

Rare Genetic Disorders

In rare cases, a genetic condition can be the cause. Transcobalamin II deficiency is a rare genetic disorder where the body cannot transport B12 in the bloodstream, leading to deficiency. Similarly, genetic mutations like MTHFR deficiency can affect the body's ability to metabolize B12 correctly, sometimes requiring special forms of supplementation.

Parasitic Infection

Infections can also be a factor. The fish tapeworm, Diphyllobothrium latum, can absorb significant amounts of B12 from the small intestine, leading to a deficiency in the host. While rare in many developed countries due to modern sanitation, it remains a possible cause.

Conclusion

Understanding the underlying cause of B12 deficiency is crucial for proper diagnosis and effective treatment. While dietary intake plays a role for vegans and vegetarians, the most common drivers involve complex malabsorption issues within the digestive system, including autoimmune disorders like pernicious anemia, effects from gastrointestinal surgery, and chronic inflammatory conditions. Pinpointing the specific problem—whether it is a lack of intrinsic factor, low stomach acid, or another issue—allows healthcare providers to create a targeted treatment plan, which often involves supplements or injections to bypass the impaired absorption pathway. Ignoring these root causes can lead to more serious and irreversible neurological and hematological complications.

For more in-depth information, the National Institutes of Health (NIH) provides comprehensive health professional fact sheets on vitamin B12.

Frequently Asked Questions

While a vegan diet can cause a B12 deficiency due to the lack of animal product intake, it is not the most common cause overall. The most frequent underlying reason is malabsorption caused by intrinsic factor issues or other digestive problems, even in people who eat meat.

Intrinsic factor is a protein secreted by the stomach that binds to vitamin B12. This binding is essential for the vitamin to be absorbed in the small intestine. Without sufficient intrinsic factor, B12 cannot be taken up by the body and is instead passed through the digestive system.

Yes, long-term use of medications that suppress stomach acid, such as proton pump inhibitors (PPIs) and H2 blockers, can interfere with B12 absorption. The stomach acid is necessary to release B12 from food proteins before it can bind with intrinsic factor.

Older adults are more prone to B12 deficiency primarily because of decreased stomach acid production, which hinders the release of B12 from food. This condition is often associated with atrophic gastritis, and it makes absorption of B12 from supplements more efficient than from food.

Pernicious anemia is an autoimmune disorder where the body's immune system attacks and destroys the stomach cells that produce intrinsic factor. With no intrinsic factor, the body cannot absorb vitamin B12 from food, leading to a deficiency.

Yes, chronic digestive conditions such as Crohn's disease and celiac disease can cause B12 deficiency by damaging the intestinal lining, particularly the ileum, where the B12-intrinsic factor complex is absorbed. Small Intestine Bacterial Overgrowth (SIBO) also affects B12 levels by having bacteria consume the vitamin.

If left untreated, B12 deficiency can lead to serious and potentially irreversible complications, including severe nerve damage (peripheral neuropathy), memory loss, cognitive issues, and megaloblastic anemia, which can strain the heart.