What is the mechanism of Vitamin B12 (Cobalamin) absorption?

From the Guidelines

Vitamin B12 absorption occurs through a complex multi-step process involving the binding of dietary B12 to R-proteins in the stomach, degradation of R-proteins by pancreatic enzymes, and subsequent binding to intrinsic factor for absorption in the terminal ileum through receptor-mediated endocytosis, as described in the espen micronutrient guideline 1. The process begins with the release of vitamin B12 from proteins in food by stomach acid and pepsin. Then, in the stomach, B12 binds to R-proteins produced by salivary glands. As this complex reaches the duodenum, pancreatic enzymes degrade the R-proteins, allowing B12 to bind with intrinsic factor (IF), a glycoprotein secreted by gastric parietal cells. Key steps in this process include:

• Release of vitamin B12 from food proteins by stomach acid and pepsin
• Binding of B12 to R-proteins in the stomach
• Degradation of R-proteins by pancreatic enzymes in the duodenum
• Binding of B12 to intrinsic factor for absorption in the terminal ileum This absorption mechanism requires adequate stomach acid, functional pancreatic enzymes, intrinsic factor production, and healthy ileal mucosa, as outlined in the espen micronutrient guideline 1. Deficiencies can occur from inadequate dietary intake, malabsorption conditions, or certain medical interventions, and can be treated with high-dose oral supplements or intramuscular injections, as recommended in guidelines such as those from the british obesity and metabolic surgery society 2.

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 main mechanism of B12 absorption is through binding to intrinsic factor in the stomach, separation in the terminal ileum, and then absorption into the mucosal cell. A small amount (about 1%) is absorbed by simple diffusion. This information is based on the drug label for methylcobalamin (PO) 3.

From the Research

Vitamin B12 Absorption Mechanism

• The absorption of vitamin B12 is a complex process involving several gene products, including carrier proteins, plasma membrane receptors, and transporters 4.
• Under physiological conditions, vitamin B12 bound to the gastric intrinsic factor is internalized in the ileum by a highly specific receptor complex composed of Cubilin and Amnionless 4.
• The process of vitamin B12 absorption can be summarized as follows: + In the stomach, B12 is released from food carrier proteins and binds to haptocorrin (HC) 5. + The degradation of HC by pancreatic proteases and the pH change trigger the transfer of B12 to intrinsic factor (IF) in the duodenum 5. + Cubilin and amnionless are the two components of the receptor that mediates the uptake of B12 in the distal ileum 4, 5.
• Vitamin B12 malabsorption can occur due to various factors, including: + Inherited disorders such as intrinsic factor deficiency, Imerslund-Gräsbeck disease, and Addison's pernicious anemia 4, 5. + Digestive diseases such as pancreatic insufficiency, obstructive jaundice, tropical sprue, and celiac disease 5. + Other causes including bacterial overgrowth, parasitic infestations, Zollinger-Ellison syndrome, inflammatory bowel diseases, and chronic radiation enteritis of the distal ileum 5.

Key Factors Involved in Vitamin B12 Absorption

• Intrinsic factor (IF): a protein produced by the stomach that binds to vitamin B12 and facilitates its absorption in the ileum 4, 5.
• Haptocorrin (HC): a protein that binds to vitamin B12 in the stomach and transfers it to intrinsic factor in the duodenum 5.
• Transcobalamin (TC): a protein that transports vitamin B12 in the bloodstream and delivers it to cells 6, 5.
• Cubilin and amnionless: receptors that mediate the uptake of vitamin B12 in the distal ileum 4, 5.

Assessment of Vitamin B12 Deficiency

• Serum B12 is still the most commonly used test for assessing vitamin B12 deficiency, but it has limitations in terms of sensitivity and specificity 6.
• Other tests such as holotranscobalamin, serum methylmalonic acid, and plasma homocysteine measurements are also used to assess vitamin B12 status 6.
• The lack of a robust absorption test makes it challenging to determine the cause of depleted B12 status and can lead to incorrect supplementation regimes 6, 5.