The Intrinsic Factor: the Key to Vitamin B12 Absorption
For vitamin B12 absorption to be possible a special glycoprotein produced by the parietal cells must also be present. This is called intrinsic factor (IF) or gastric intrinsic factor (GIF).
Vitamin B12 is mostly bound to proteins in food and is separated by specific enzymes in the stomach. It is then transported to the small intestine by a different transport protein called haptocorrin, where it binds to intrinsic factor. IF transports the B12 to receptors in the intestinal mucosa, where the vitamin can then gain access to the mucosal cells.
There is a limited number of intrinsic factor receptors, meaning that only around 1.5µg of B12 per meal can be absorbed in this way. A further 1% of the dosage is absorbed via passive diffusion, bypassing the need for intrinsic factor. Because the absorption figure is only 1%, this method is only effective when much higher vitamin B12 doses are consumed.1,2
The Intrinsic Factor – Limiting the Amount of B12 Absorbed
Because foods tend to contain just small amounts of vitamin B12, it is vitally important that the vitamin is maximally exposed to intrinsic factor as it makes its way through the digestive system, to allow adequate B12 absorption from the diet. Without intrinsic factor the likelihood of obtaining a B12 supply to sufficient cover the body’s requirements just from foods is extremely low.
Intrinsic factor even affects how vitamin B12 supplements should be taken: 3-10µg dosages should be administered at intervals throughout the day in order to optimise B12’s uptake via IF. Since this is likely quite inconvenient for most people and potentially unreliable, most supplements are dosed highly enough to allow for sufficient absorption via passive diffusion. This has been calculated at around 200µg in most cases.
How is the Intrinsic Factor Produced?
In the human body intrinsic factor by the parietal cells of the stomach. If this secretion is disturbed in anyway and there is a lack of intrinsic factor, a vitamin B12 deficiency is likely to arise.
The most common cause of B12 malabsorption is atrophic gastritis (type A gastritis), a chronic gastritis and autoimmune disorder in which the body produces antibodies that attack and destroy parietal cells that secrete IF.
A lack of intrinsic factor can also be the result of surgery that involves the removal of parts of the stomach (gastric resection, gastrectomy). Alcoholism is also known to affect the production of intrinsic factor, as the stomach becomes inflamed.
The Intrinsic Factor Antibody
There are other autoimmune disorders that impair the uptake of vitamin B12 by intrinsic factor. In these IF antibodies attack. Two types are distinguished:
Intrinsic factor blocking antibody (Type 1): Antibodies that prevent B12 from binding to intrinsic factor.
Intrinsic factor binding antibody (Type 2): Antibodies that bind to the B12 and intrinsic factor complex, preventing this complex from attaching to receptors at the binding site in the small intestine.
Antibodies to parietal cells and intrinsic factor antibodies can both be detected using testing methods.
The Consequences of an Intrinsic Factor Deficiency
If intrinsic factor levels are low, the symptoms of a vitamin B12 deficiency can result, the most serious of these being pernicious anemia and funicular myelosis (demylinating disease affecting the spinal cord).
The Intrinsic Factor and Calcium
In order for intrinsic factor to bind to receptors in the small intestine calcium is must also be present. If this mineral is absent then B12 cannot be absorbed despite sufficient intrinsic factor levels.
This is particularly important for diabetics being treated with metformin. This medicine is known to diminish calcium levels in intestine, which is why many metformin users eventually develop a vitamin B12 deficiency. Such negative side effects can be prevented through the administration of high dosage B12 supplements (300-1000 µg) absorbed directly via passive diffusion. Studies have also shown that high doses of calcium can have a reparative effect too.3
It makes sense then, that some vitamin B12 supplements also containing calcium have been shown to optimise absorption.
The Intrinsic Factor Test
The Schilling test can determine whether there are sufficient intrinsic factor levels present. The patient is given radiolabeled B12 to consume so that absorption can be measured. If an abnormality is found a second test takes place in which both radiolabeled B12 and intrinsic factor are administered. If the results show an increased absorption of B12 then a lack of intrinsic factor is evident.
Typically, the Schilling test is only performed in cases of severe B12 deficiency or when pernicious anemia is suspected, in order to identify a cause.
The Intrinsic Factor in Vegetarian and Vegan Diets
The highest concentrations of B12 are found in meat products. Larger amounts are found in offal and muscle meat and lesser amounts are found in egg and dairy products. A lower B12 food concentration increases the need for intrinsic factor absorption. The absorption method can become impaired through high consumption of dairy products, which is a common feature of vegetarian diets. If this is the case then vitamin B12 supplements should be taken. For vegans supplements are generally always necessary.
1 Abels, J., Vegter, J. J. M., Woldring, M. G., Jans, J. H. and Nieweg, H. O. (1959), The Physiologic Mechanism of Vitamin B12 Absorption. Acta Medica Scandinavica, 165: 105–113. doi: 10.1111/j.0954-6820.1959.tb14477.x
2 Berlin, H., Berlin, R. and Brante, G. (1968), Oral Treatrment Of Pernicious Anemia With High Doses Of Vitamin B12 Without Intrinsic Factor. Acta Medica Scandinavica, 184: 247–258. doi: 10.1111/j.0954-6820.1968.tb02452.x
3 Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care. 2000 Sep;23(9):1227-31. PubMed PMID: 10977010.