How is vitamin B12 absorbed? A detailed breakdown

November 30, 2025 •

2 min read

The absorption of vitamin B12 is a remarkably complex process, with its bioavailability varying significantly depending on the food source. The intricate mechanism ensures this vital nutrient, essential for nerve function and DNA synthesis, is efficiently extracted from our diet, but it requires a perfectly functioning digestive system.

Quick Summary

This article explains the multi-stage process of vitamin B12 absorption, detailing the roles of stomach acid, binding proteins like intrinsic factor, and specific receptors in the small intestine. It also covers common issues that can lead to malabsorption and deficiency.

Key Points

Initial Release: Vitamin B12 is freed from food proteins by stomach acid and digestive enzymes like pepsin.
Binding Partners: After being freed, B12 binds first to haptocorrin and later, in the duodenum, switches to bind with intrinsic factor.
Terminal Ileum: The active absorption of the B12-intrinsic factor complex occurs specifically in the terminal ileum, the final part of the small intestine.
Two Absorption Paths: There are two methods of absorption: an efficient, intrinsic factor-dependent active pathway for small amounts, and a less efficient passive diffusion for larger supplemental doses.
Common Malabsorption Causes: Impaired absorption can result from lack of stomach acid, autoimmune conditions like pernicious anemia, and certain medications like metformin.
Key Transport Protein: Post-absorption, B12 is carried through the bloodstream by another protein, transcobalamin II, to be delivered to body tissues.

The multi-stage journey of vitamin B12 absorption

Vitamin B12 (cobalamin) absorption is a complex process in the gastrointestinal tract. It starts upon ingestion and finishes in the terminal ileum.

Step 1: Release from food proteins in the stomach

Vitamin B12 in food is bound to protein. In the stomach, hydrochloric acid and pepsin release B12 from its protein complex. Low stomach acid impairs this step.

Step 2: Binding to haptocorrin and intrinsic factor

Free B12 first binds to haptocorrin in the stomach, protecting it from the acid. Parietal cells also secrete intrinsic factor (IF), which will bind to B12 later.

Step 3: Transition to the duodenum and ileum

In the duodenum, pancreatic enzymes break down haptocorrin, freeing B12 to bind with intrinsic factor. The B12-IF complex is crucial for later absorption.

Step 4: Final absorption in the ileum

The B12-IF complex reaches the terminal ileum and attaches to specific receptors. This triggers receptor-mediated endocytosis, internalizing the complex into intestinal cells. Inside the cells, B12 separates from IF and enters the bloodstream, transported by transcobalamin II to the liver and other tissues.

Comparison of Active vs. Passive Absorption

Active absorption relies on intrinsic factor and ileal receptors, efficiently absorbing small amounts of B12. Passive diffusion absorbs only 1-2% of a dose directly through the intestinal wall, effective only with high supplemental doses.


Feature	Active (Intrinsic Factor) Absorption	Passive Diffusion Absorption
Route	Relies on intrinsic factor and specific ileal receptors	Diffuses directly through intestinal cell walls
Efficiency	Highly efficient but saturable at doses over 1-2 mcg	Very inefficient, absorbs only ~1-2% of a dose
Requirement	Requires healthy stomach acid and intrinsic factor production	No requirement for intrinsic factor or stomach acid
Capacity	Limited capacity, maxes out at very low doses	Effective only with very high, pharmacological doses of B12
Relevance	Primary method for dietary B12 intake	Secondary pathway, used mainly for high-dose supplements

Factors that impair absorption

Several conditions can impair B12 absorption:

Pernicious Anemia: Autoimmune attack on intrinsic factor-producing cells.
Atrophic Gastritis: Stomach lining thinning reduces acid and intrinsic factor.
Gastrointestinal Surgery: Alters stomach or ileum sections involved in B12 processing.
Digestive Disorders: Crohn's, celiac, or pancreatitis can damage the ileum.
Medications: Metformin and acid-reducers can interfere.
Dietary Factors: Vegan/vegetarian diets may lack B12 from animal sources.

Conclusion

Vitamin B12 absorption is a detailed process involving release by stomach acid and uptake in the ileum via intrinsic factor. While passive diffusion exists for high doses, the active pathway is key for dietary intake. Disruptions from various conditions, medications, or diets can lead to deficiency. Understanding these steps is vital for preventing and treating B12 deficiency.

For more detailed information, the National Institutes of Health provides a comprehensive fact sheet on vitamin B12, detailing its functions, food sources, and absorption pathways.

Frequently Asked Questions

Intrinsic factor is a protein made by the stomach's parietal cells that is necessary for vitamin B12 absorption. It binds to B12 in the duodenum, forming a complex that protects the vitamin and enables its recognition and uptake by receptors in the terminal ileum.

Stomach acid, or hydrochloric acid, is crucial for separating vitamin B12 from the protein it is bound to in food. Without sufficient stomach acid, this initial release cannot occur, preventing the vitamin from binding to intrinsic factor and being absorbed effectively.

Yes, a very small percentage (1-2%) of B12 can be absorbed without intrinsic factor through a process called passive diffusion. This is the principle behind high-dose oral B12 supplements, which are designed to force enough of the vitamin across the intestinal wall to be effective, even if the primary absorption route is blocked.

Once absorbed from the ileum, vitamin B12 is released from the intrinsic factor complex and attaches to another protein called transcobalamin II. This new complex then circulates in the blood, delivering the vitamin to the liver for storage and other body tissues for use.

Conditions that cause poor B12 absorption include pernicious anemia, atrophic gastritis, Crohn's disease, celiac disease, and gastrointestinal surgery. Additionally, long-term use of certain medications like metformin and acid-reducing drugs can impair absorption.

B12 injections are used when a person has a severe malabsorption problem, such as pernicious anemia, that prevents the efficient oral absorption of B12. Since injections bypass the digestive system entirely, they ensure the vitamin reaches the bloodstream directly.

B12 found in supplements and fortified foods is typically in its free, unbound form, which means it doesn't need to be separated from proteins by stomach acid before binding to intrinsic factor. This can make B12 from supplements more readily absorbed by some individuals, especially those with reduced stomach acid.