From the FDA Drug Label
Gastrointestinal absorption of vitamin B12 depends on the presence of sufficient intrinsic factor and calcium ions. Vitamin B12 is bound to intrinsic factor during transit through the stomach; separation occurs in the terminal ileum in the presence of calcium, and vitamin B12 enters the mucosal cell for absorption It is then transported by the transcobalamin binding proteins. A small amount (approximately 1% of the total amount ingested) is absorbed by simple diffusion, but this mechanism is adequate only with very large doses.
The steps of B12 absorption are:
- Binding to intrinsic factor in the stomach
- Separation from intrinsic factor in the terminal ileum with calcium
- Entry into the mucosal cell for absorption
- Transport by transcobalamin binding proteins Additionally, a small amount can be absorbed by simple diffusion. 1
From the Research
Vitamin B12 absorption involves several key steps, including binding to haptocorrin in the stomach, release by pancreatic enzymes in the duodenum, and absorption in the terminal ileum via intrinsic factor and cubilin receptors, as described in studies such as 2. The process of vitamin B12 absorption is complex and requires multiple components to function properly.
- First, dietary vitamin B12 from animal products enters the stomach, where it binds to haptocorrin (R-protein) produced by salivary glands, protecting it from stomach acid.
- In the duodenum, pancreatic enzymes release vitamin B12 from haptocorrin, allowing it to bind to intrinsic factor (IF), which is secreted by gastric parietal cells.
- This vitamin B12-IF complex travels through the small intestine to the terminal ileum, where specific receptors (cubilin) on ileal enterocytes recognize and facilitate absorption of the complex.
- Once inside enterocytes, vitamin B12 is released and transferred to transcobalamin II for transport in the bloodstream to tissues throughout the body. This complex process requires normal gastric acid production, adequate intrinsic factor, healthy pancreatic function, and intact ileal receptors, as noted in 3. Disruption at any step can lead to vitamin B12 deficiency, which explains why conditions like pernicious anemia (lack of intrinsic factor), gastrectomy, pancreatic insufficiency, or ileal disease can impair vitamin B12 absorption and necessitate supplementation, often through parenteral routes that bypass these digestive steps, as discussed in 4 and 5. The most recent and highest quality study, 2, provides a comprehensive overview of the diagnosis, treatment, and long-term management of vitamin B12 deficiency, highlighting the importance of recognizing clinical symptoms and using serum vitamin B12 levels and methylmalonic acid or homocysteine to support diagnosis. Additionally, studies such as 6 have investigated the role of pernicious anemia in patients with vitamin B12 deficiency and the efficacy of oral vitamin B12 replacement therapy, finding that oral replacement therapy can be effective even in patients with pernicious anemia. Overall, understanding the steps involved in vitamin B12 absorption is crucial for diagnosing and managing vitamin B12 deficiency, and recent studies such as 2 provide valuable guidance on the best approaches to diagnosis and treatment.