Intrinsic Factor: The Protein, Not The Vitamin, Needed to Absorb Vitamin B12

October 29, 2025 •

3 min read

Between 3% and 43% of older adults may have a vitamin B12 deficiency due to a decrease in their body's ability to absorb it. Contrary to common belief, the crucial substance needed to absorb vitamin B12 is not another vitamin but a protein produced in the stomach called intrinsic factor.

Quick Summary

The body requires a protein called intrinsic factor to properly absorb vitamin B12 from food and supplements, primarily in the small intestine. A deficiency in this protein, often caused by autoimmune conditions like pernicious anemia, leads to malabsorption and can result in severe health issues.

Key Points

Intrinsic Factor is a Protein: The substance required to absorb vitamin B12 is a protein called intrinsic factor, not a vitamin.
Intrinsic Factor is Stomach-Made: The parietal cells lining the stomach produce and secrete intrinsic factor.
Autoimmune Attack Causes Deficiency: Pernicious anemia is an autoimmune disease where the body attacks and destroys the cells that produce intrinsic factor, leading to severe B12 malabsorption.
Absorption is a Multi-Step Process: The process involves B12 binding first to haptocorrin, then to intrinsic factor, before being absorbed in the small intestine.
Other Factors Affect Absorption: Conditions like Crohn's disease, gastric surgery, and certain medications can impair B12 absorption.
High Oral Doses Offer Passive Absorption: For those with intrinsic factor deficiency, very high oral doses can be absorbed via passive diffusion, though this method is far less efficient.
Folate Can Mask Symptoms: High folate intake can sometimes hide the signs of B12 deficiency, potentially allowing for the progression of neurological damage.

The Surprising Truth About B12 Absorption

Vitamin B12 (cobalamin) absorption relies on a specific protein, not another vitamin. Intrinsic factor (IF), a glycoprotein made by parietal cells in the stomach, binds to B12, facilitating its absorption into the bloodstream. A lack of intrinsic factor is the main cause of pernicious anemia, a B12 deficiency that can cause significant health problems.

The Multi-Step Process of Vitamin B12 Absorption

B12 absorption involves several digestive steps:

Release from Food: Stomach acid and enzymes free B12 from food proteins. This step is unnecessary for B12 in fortified foods or supplements.
Binding with Haptocorrin: Free B12 binds to haptocorrin, protecting it in the stomach's acidic environment.
Transfer to Intrinsic Factor: In the small intestine, haptocorrin is broken down, and B12 binds to intrinsic factor.
Ileal Absorption: The intrinsic factor–B12 complex travels to the terminal ileum where receptors absorb it into the bloodstream.
Transport into the Body: Transcobalamin II then transports B12 to cells throughout the body.

Factors That Inhibit Intrinsic Factor and B12 Absorption

Several conditions can impair B12 absorption:

Autoimmune Attack: Pernicious anemia, an autoimmune condition, destroys parietal cells, leading to a lack of intrinsic factor.
Gastric Surgery: Procedures like gastric bypass can reduce parietal cells and intrinsic factor production.
Chronic Conditions: Diseases such as Crohn's and celiac disease can damage the ileum, hindering absorption.
Medications: PPIs and H2 blockers can reduce stomach acid, impairing B12 release from food.
Bacterial Overgrowth: SIBO and certain infections can lead to bacteria consuming B12 before it's absorbed.

Can Other Vitamins Help B12 Absorption?

No other vitamin directly replaces intrinsic factor. However, some nutrients interact with B12:

Folate (Vitamin B9): Folate and B12 work together in metabolic processes. High folate can mask B12 deficiency symptoms, potentially delaying diagnosis and allowing neurological damage.
Vitamin D: Some studies link low vitamin D to low B12, possibly due to vitamin D's effect on the gastric lining.

Comparing Absorption Pathways

Different methods of B12 absorption exist:


Feature	Normal Absorption (Intrinsic Factor)	Passive Diffusion	Injections (Bypassing GI Tract)
Mechanism	Active, receptor-mediated uptake requiring intrinsic factor.	Very low efficiency, passive uptake through the intestinal wall.	Direct administration into the muscle, bypassing the digestive system entirely.
Efficiency	Highly efficient for typical dietary amounts.	Only absorbs about 1-2% of the oral dose.	100% systemic bioavailability.
Dosage Requirements	Standard dietary or supplemental doses are sufficient.	Requires very high oral doses (1000-2000 mcg) to absorb a small, effective amount.	Prescribed doses based on the severity of deficiency.
Use Case	Most healthy individuals absorbing B12 from food or supplements.	Used for those with intrinsic factor deficiency who opt for oral treatment.	Essential for those with pernicious anemia or severe malabsorption issues.

Conclusion

Intrinsic factor, a protein, is essential for vitamin B12 absorption. Disruptions to this process, like those caused by pernicious anemia or gastric surgery, can lead to deficiency. High-dose oral supplements or injections can provide B12 by bypassing the intrinsic factor pathway. Consulting a healthcare professional is crucial for diagnosis and treatment of B12 deficiency.

What vitamin is needed to absorb vitamin B12? Learn the truth.

For more information on vitamin B12, its functions, and dietary sources, visit the National Institutes of Health Office of Dietary Supplements.(https://ods.od.nih.gov/factsheets/VitaminB12-Consumer/)

Frequently Asked Questions

Intrinsic factor is a glycoprotein (a protein with a sugar component) produced and secreted by the parietal cells in the lining of your stomach.

Intrinsic factor is essential because it binds to vitamin B12 in the digestive tract, forming a complex that protects B12 from degradation and allows it to be recognized and absorbed by receptors in the small intestine.

Pernicious anemia is an autoimmune disorder in which the immune system attacks and destroys the parietal cells in the stomach. This results in a lack of intrinsic factor, which is required to absorb vitamin B12.

With sufficient oral supplementation, a small amount (around 1-2%) of vitamin B12 can be absorbed via passive diffusion, bypassing the need for intrinsic factor. However, this method is inefficient compared to the intrinsic factor pathway.

Besides pernicious anemia, other causes include gastric surgeries, Crohn's or celiac disease, bacterial overgrowth in the small intestine, and certain medications that reduce stomach acid.

No, a standard multivitamin dose is usually not enough for individuals lacking intrinsic factor. Very high-dose oral supplements or injections are typically needed to compensate for the inefficiency of passive absorption.

While other B vitamins, including folate, interact with B12 in metabolic processes, they do not facilitate its initial absorption via the intrinsic factor pathway. High folate intake can sometimes mask a B12 deficiency, which can be dangerous.