Intrinsic Factor: The Key Factor Required for B12 Absorption

December 2, 2025 •

2 min read

Intrinsic factor is a protein produced by parietal cells in the stomach that is absolutely essential for the body to absorb vitamin B12. Without a sufficient amount of this specific glycoprotein, the vital nutrient cobalamin cannot be absorbed in the small intestine, leading to potentially serious health issues like pernicious anemia.

Quick Summary

Intrinsic factor, a protein made in the stomach, is necessary for absorbing vitamin B12 in the small intestine. A deficiency can cause severe health problems.

Key Points

Essential Protein: Intrinsic factor is a glycoprotein crucial for the body's absorption of vitamin B12.
Stomach-Produced: It is secreted by the parietal cells in the lining of the stomach.
Binding and Protection: Intrinsic factor binds to vitamin B12 in the digestive tract, protecting it from degradation.
Absorption Site: The IF-B12 complex is absorbed by specific receptors in the terminal ileum of the small intestine.
Malabsorption Causes: A lack of intrinsic factor, due to conditions like pernicious anemia or gastric surgery, is a leading cause of B12 deficiency.
Alternative Pathway: A small amount of B12 can be absorbed via passive diffusion, especially with very high supplemental doses, bypassing the need for intrinsic factor.

What Is Intrinsic Factor?

Intrinsic factor (IF) is a glycoprotein produced by parietal cells in the stomach lining. Its main job is to bind with vitamin B12 after it's released from food. This complex is protected as it travels to the small intestine for absorption. A lack of intrinsic factor is the most common reason for B12 deficiency in adults.

The Role of Stomach Acid and Enzymes

Vitamin B12 is released from food in the stomach by hydrochloric acid and pepsin. It first binds to haptocorrin, protecting it in the stomach's acidic environment.

The Journey to the Small Intestine

In the small intestine, haptocorrin is broken down, freeing B12 to bind with intrinsic factor. This IF-B12 complex is then ready for absorption.

Absorption in the Ileum

The IF-B12 complex reaches the terminal ileum where specific receptors absorb it into intestinal cells. B12 is then transported into the bloodstream by transcobalamin II.

Factors That Impair Intrinsic Factor Function and Production

Problems with intrinsic factor can lead to B12 deficiency and pernicious anemia. Causes include:

Autoimmune atrophic gastritis (Pernicious Anemia): The immune system attacks parietal cells that make intrinsic factor.
Gastric Surgery: Removal of part or all of the stomach reduces intrinsic factor production.
Chronic Alcoholism: Can damage the stomach lining.
Certain Medications: Some acid-reducing drugs can hinder B12 release from food.

A Comparison of Absorption Pathways

While intrinsic factor is key for normal B12 absorption, a small amount can be absorbed differently.


Feature	Intrinsic Factor-Dependent Absorption	Passive Diffusion Absorption
Mechanism	Specific transport after binding with intrinsic factor.	Non-specific movement across the intestinal lining.
Efficiency	Highly efficient for small B12 doses.	Very inefficient, absorbing only a small percentage.
Requirement	Requires intrinsic factor.	Does not require intrinsic factor.
Location	Terminal ileum.	Throughout the small intestine.
Clinical Relevance	For B12 from food and low-dose supplements.	Used for treating intrinsic factor deficiency with high doses.

Conclusion

Intrinsic factor is vital for the proper absorption of vitamin B12. Produced in the stomach, it binds to B12, allowing its uptake in the small intestine. Conditions like pernicious anemia, which destroy intrinsic factor-producing cells, demonstrate its importance. For those lacking intrinsic factor, high-dose B12 can be absorbed via a less efficient pathway. Understanding this process is crucial for managing B12 deficiency. For further information, consult resources like the NIH.

Frequently Asked Questions

Intrinsic factor is produced by the parietal cells, which are located within the lining of the stomach.

If you lack intrinsic factor, you cannot absorb vitamin B12 properly. This leads to a B12 deficiency, which can cause pernicious anemia and potentially severe neurological problems.

A small amount of B12 can be absorbed without intrinsic factor through passive diffusion, especially when high-dose supplements are taken. This is why injections or high-dose oral supplements are used for people with pernicious anemia.

Pernicious anemia is an autoimmune disease where the body's immune system attacks and destroys the parietal cells that produce intrinsic factor, leading to a severe B12 deficiency.

Some medications, like long-term proton pump inhibitors (PPIs), can reduce stomach acid, which hinders the initial release of B12 from food. While they don't directly stop intrinsic factor production, they can still lead to B12 deficiency.

In the stomach, hydrochloric acid and the enzyme pepsin work together to separate the vitamin B12 from the protein it is bound to in food.

Haptocorrin is a protein in saliva that binds to B12 in the stomach, protecting it from stomach acid. In the small intestine, it is degraded by pancreatic enzymes, allowing intrinsic factor to bind to B12.