How does the body metabolize vitamin B12? A step-by-step guide to absorption and cellular function

October 9, 2025 •

3 min read

Unlike most other vitamins, approximately 50% of the body's total vitamin B12 is stored in the liver, with reserves that can last for years. This long storage is a testament to the complex process of how does the body metabolize vitamin B12?, a journey that involves a cast of crucial proteins.

Quick Summary

The body metabolizes vitamin B12 through a complex pathway involving multiple protein carriers, beginning with its release from food in the stomach, binding to intrinsic factor, and absorption in the small intestine before transport and activation inside cells.

Key Points

Initial Release: Stomach acid and enzymes separate vitamin B12 from food proteins, where it initially binds to the protective haptocorrin.
Intrinsic Factor Binding: Pancreatic enzymes release B12 from haptocorrin in the small intestine, allowing it to bind with intrinsic factor secreted by the stomach's parietal cells.
Targeted Absorption: The B12-intrinsic factor complex travels to the terminal ileum, where it is specifically absorbed into the body via the cubam receptor.
Blood Transport: Absorbed B12 is bound to transcobalamin II for transport through the bloodstream, enabling its delivery to cells throughout the body.
Cellular Activation: Inside the cells, B12 is converted into its active coenzyme forms, methylcobalamin and adenosylcobalamin, which are crucial for DNA synthesis and fat/amino acid metabolism.
Deficiency Risk: Many factors can disrupt this process, including autoimmune conditions (pernicious anemia), gastric surgery, digestive diseases, and restrictive diets, leading to deficiency symptoms.

The multi-stage journey of vitamin B12

Metabolizing vitamin B12, or cobalamin, is far from a simple task. This water-soluble vitamin requires the help of several proteins and a well-functioning digestive system to be properly absorbed and used by the body. This intricate, multi-stage process ensures that this essential nutrient, vital for nerve function, DNA synthesis, and red blood cell formation, reaches its intended cellular destination. A breakdown at any point in this pathway can lead to a deficiency, even with adequate dietary intake.

Stage 1: Digestion and release in the stomach

The metabolism of vitamin B12 begins in the stomach, where ingested B12, typically bound to food proteins, is released. Salivary glands produce haptocorrin to protect the B12 as it travels through the digestive tract. In the stomach's acidic environment, hydrochloric acid and pepsin detach B12 from food proteins. The free B12 then binds to haptocorrin. Simultaneously, parietal cells in the stomach secrete intrinsic factor, which remains unbound in the stomach.

Stage 2: Binding to intrinsic factor in the duodenum

In the duodenum, pancreatic proteases break down haptocorrin, freeing the B12. This free B12 then binds to intrinsic factor, forming a complex resistant to digestion.

Stage 3: Absorption in the ileum

The B12-intrinsic factor complex moves to the terminal ileum, where the cubam receptor facilitates its absorption into ileal cells via receptor-mediated endocytosis. High-dose oral B12 can also be absorbed inefficiently through passive diffusion.

Stage 4: Transport and cellular delivery

Inside the intestinal cells, the B12-intrinsic factor complex breaks down, and B12 binds to transcobalamin II (TC2), forming holoTC. HoloTC is the active form transported in the bloodstream to body cells, including the liver for storage.

Stage 5: Intracellular metabolism

Upon entering a cell, the holoTC complex is internalized and degraded in lysosomes, releasing B12. B12 is then converted into its active forms, adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), which act as cofactors for enzymes.

The final metabolic reactions

MeCbl is crucial for methionine synthase, an enzyme vital for converting homocysteine to methionine and synthesizing DNA. AdoCbl is a cofactor for methylmalonyl-CoA mutase, involved in fat and amino acid metabolism. Disruption of these processes can lead to conditions like megaloblastic anemia or accumulation of methylmalonic acid.

Factors affecting absorption and metabolism

Various factors can hinder B12 metabolism. Pernicious anemia, an autoimmune condition affecting intrinsic factor production, is a common cause of deficiency. Other factors include dietary deficiencies (e.g., vegan diets), digestive disorders like Crohn's or celiac disease, gastric surgery, certain medications, and age-related decreases in stomach acid and intrinsic factor.

Comparison of B12 absorption methods


Feature	Active Absorption (Intrinsic Factor)	Passive Diffusion
Mechanism	B12 binds to intrinsic factor (IF) and is absorbed via specific receptors (cubam) in the terminal ileum.	B12 diffuses directly through the intestinal wall, independent of a transport system.
Location	Primarily occurs in the terminal ileum.	Occurs along the entire length of the intestine.
Efficiency	Highly efficient, but saturable, with a capacity of about 1-2 mcg per meal.	Very inefficient, absorbing less than 1-5% of the total dose.
Supplementation	The physiological method for absorbing B12 from food.	The primary mechanism for absorbing high-dose oral supplements, bypassing the need for intrinsic factor.
Requirement for IF	Absolutely dependent on intrinsic factor.	Does not require intrinsic factor.

Conclusion

Vitamin B12 metabolism is a complex process involving multiple protein interactions in the digestive system and within cells. Each stage is essential, from initial release from food and binding to intrinsic factor for absorption in the ileum, to transport by transcobalamin and conversion to active coenzymes within cells. Understanding how does the body metabolize vitamin B12? helps identify the various factors that can lead to deficiency, such as dietary restrictions, medical conditions, and certain medications. While the liver stores a significant amount of B12, prolonged issues in metabolism will eventually result in deficiency and health problems. This highlights why alternative treatments like injections or high-dose oral supplements are necessary when the natural absorption pathway is compromised. The National Institutes of Health provides further details on vitamin B12 metabolism.(https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/)

Frequently Asked Questions

Intrinsic factor is a protein secreted by the parietal cells in the stomach. It is crucial because it binds to vitamin B12 in the small intestine, forming a complex that is necessary for the vitamin's absorption in the terminal ileum.

Yes, but only in very small quantities and with extremely low efficiency. Passive diffusion allows for the absorption of about 1-5% of a large oral dose of B12, bypassing the need for intrinsic factor. This is why high-dose oral supplements can be effective for those with intrinsic factor deficiency.

The two active forms are methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). MeCbl is a cofactor for methionine synthase, needed for DNA synthesis. AdoCbl is a cofactor for methylmalonyl-CoA mutase, which is involved in fat and amino acid metabolism.

Because the liver can store a significant amount of vitamin B12, it can take several years for a deficiency to develop in healthy individuals with poor dietary intake. However, for those with malabsorption issues, symptoms can appear much sooner, within months to a year.

Genetic disorders affecting intracellular processing, such as those related to the MMACHC gene, can prevent the proper conversion of B12 into its active coenzymes, leading to metabolic abnormalities like homocystinuria and methylmalonic aciduria.

After absorption, vitamin B12 is transported in the blood bound primarily to transcobalamin II (TC2), forming a complex called holoTC. Another protein, haptocorrin, also binds B12 in circulation, but the B12 bound to TC2 is the form readily delivered to body cells.

As people age, their production of stomach acid tends to decrease, which impairs the release of B12 from food proteins. This reduced absorption, even with adequate intake, puts the elderly at a higher risk of developing a deficiency.