Vitamin B12 Absorption
Understanding vitamin B12 absorption can help with understanding causes of vitamin B12 deficiency.
(1) Dietary vitamin B12 is normally bound to proteins in food and is provided by food products of animal origin.
(2) Pepsin and acid pH in the stomach will degrade these food proteins and release vitamin B12.
(3) The vitamin B12 that is now free then binds to one of the three vitamin B12 binding proteins, called haptocorrin, which is produced by the salivary glands and the parietal cells in the stomach. In the duodenum the pH is now less acidic and this allows pancreatic proteases to degrade the haptocorrin, and vitamin B12 (both newly ingested and from the bile duct) is released again and binds tightly to Intrinsic Factor produced by parietal cells.
(4) In the mucosal cells of the distal ileum the vitamin B12-Intrinsic Factor complex is recognised by special receptors.
(5) Vitamin B12 then enters the blood bound to another binding protein, transcobalamin, the complex is known as holotranscobalamin (Active B12). The majority of vitamin B12 (70-80%) in blood is bound to haptocorrin and only a minor proportion (20-30%) is bound to transcobalamin.
(6) Holotranscobalamin (Active B12) is the biologically active fraction of vitamin B12 in the blood as it is in only this form that vitamin B12 is delivered to all the cells of the body.
(7) Vitamin B12 absorbed in the intestine subsequently gets transported to the liver via the portal system.
(8) There is extensive enterohepatic circulation of vitamin B12 and B12 is transported from the liver, via the bile duct, to the duodenum.
What could possibly go wrong ?
We can see immediately that a diet that does not include food products of animal origin, or where meat is avoided, would lead to a higher risk of vitamin B12 deficiency. It should be said though that a dietary cause is a relatively rare reason. More common is malabsorption due to a number of gastrointestinal conditions:
- Atrophic gastritis, which increases with age, impairs the production of acid and enzymes needed to break down food and also the production of intrinsic factor.
- Malabsorption would also occur with pancreatic insufficiency and of course any surgery which removed part of the stomach or ileum would increase risk.
- Intestinal diseases such as Crohn's, and coeliac disease can cause problems.
- Long-term use of acid suppressants (proton pump inhibitors, H2 antagonists) is a potential risk factor, and these are some of the most widely prescribed and used drugs in the elderly population.
- Finally, in true pernicious anaemia where there is an autoimmune component, there are three different types of antibodies that could be the cause. Those which bind to the intrinsic factor-vitamin B12 complex preventing uptake, antibodies which bind to intrinsic factor itself preventing binding with vitamin B12, and antibodies to gastric parietal cells preventing the production of intrinsic factor.
See the Symptoms and At Risk Groups page for more details..
B12 LEVELS FALSELY ELEVATED IN PERNICIOUS ANAEMIA
A new publication has demonstrated that five different Total B12 assays gave normal B12 results in a patient with confirmed pernicious anaemia. To access the paper click here.
EXPERTS AGREEMENT ON UTILITY OF ACTIVE-B12
An experts meeting at a recent conference produced a Consensus Statement on the improved utility of the Active-B12 assay over Total B12. To see the statement click here.