Vitamin B12 and the Intrinsic Factor

Vitamin B12 and the Intrinsic Factor

Vitamin B12 is available in animal products as a purified coenzyme for cell enzymes. To perform this process, the vitamin B12 molecule must cross the the small intestine. This crucial step can only be done with a specific transport due to the size of the B12 molecule.

A protein known as ‘intrinsic factor’ is in charge of this task. Then, the vitamin B12 molecule will become available to the cells of the body. Therefore, if the intrinsic factor is missing, the only way to absorb vitamin B12 will be through passive diffusion.

How does the intrinsic factor work?

Vitamin B12 binds to the protein and peptides that we eat. Then, our saliva and stomach acid dissolve it during the digestion. A low gastric pH will improve the release of vitamin B12. Afterwards, vitamin B12 binds to the R protein from the saliva and stomach acid. [1] [2]

Although the R protein has a powerful effect on vitamin B12, the intrinsic factor provides a better absorption of vitamin B12. For example, there are vitamins that are analogous to vitamin B12 that are also bound to the R protein, but not to the intrinsic factor. In turn, the latter binds to a receptor (called the ileum) that channels its absorption at the end of the small intestine.

Where is the intrinsic factor produced?

The parietal cells of the stomach are in charge of producing the intrinsic factor. In fact, they produce large quantities, to the point that they exceed our requirements. Yet, we do not know why this happens. Although some believe that this improves the absorption of vitamin B12.

Vitamina B12 factor intrínseco

What happens when the intrinsic factor is not produced?

Sometimes, the body does not produce the intrinsic factor due to different reasons:

  • Hereditary absence of the intrinsic factor.
  • Moreover, there can be a mutation of the gene that encodes the intrinsic factor. Consequently, this results in an hereditary intrinsic factor deficiency (HIFD). This produces an autosomal recessive genetic disease in which each parent inherits a defective genetic copy.
  • The Imerslund-Gräsbeck syndrome is a disease that is similar to HIFD and it basically involves a malabsorption of vitamin B12. Both hereditary diseases share the typical symptoms of a vitamin B12 deficiency. For instance, gastrointestinal discomfort, pancytopenia (lack of blood cells) and anemia. Actually, we can diagnose an intrinsic factor deficiency by analyzing specific antibodies. The treatment for both diseases consists of taking vitamin B12 regularly. [3] [4]
  • A high dose will be enough to treat a vitamin B12 deficiency when we lack the intrinsic factor. In this case, the absorption mechanism relies on the passive diffusion of vitamin B12 through the intestinal membrane. The dose of vitamin B12 should be quite high (1000 mg to 2000 mg per day) since our body will be able to use around a 1.2% of the vitamin through diffusion. [5] [6]

Autoimmune reaction against the intrinsic factor

Pernicious anemia is an autoimmune disease that occurs when the organism produces antibodies that target the intrinsic factor. In fact, said antibodies bind to the intrinsic factor and prevent it from binding to vitamin B12. [7]

An insufficient production of the intrinsic factor

When the body does not produce enough intrinsic factor, it cannot absorb the necessary amount of vitamin B12. Consequently, an inadequate production of intrinsic factor can happen in the following cases:

  • As we age.
  • An analysis of the concentration of intrinsic factor in individuals over the age of 70 revealed that approximately 1% to 2% did not produce enough. [8]
  • Due to the lack of function of the parietal cells.
  • The intrinsic factor is produced in the parietal cells of the stomach. So, when we suffer certain diseases, these cells are affected and they excrete very little stomach acid, pepsin and intrinsic factor. For example, a 40% of AIDS patients that were studied did not produce enough intrinsic factor. [9]
  • Due to a surgery on the gastrointestinal tract.
  • During certain surgeries, such as a gastric bypass or gastrectomy (partial removal of the stomach). Moreover, the loss of parietal cells reduces or eliminates the production of the intrinsic factor.

The intrinsic factor and infections

The connection between the intrinsic factor and bacterial infections is reciprocal. On the one hand, the bacteria hinder the absorption of vitamin B12 by interacting with the intrinsic factor. On the other hand, the intrinsic factor plays an important role in protecting us against infections.

Helicobacter pylori bacteria, a common cause of gastric ulcers, produces an autoimmune reaction against the parietal cells and intrinsic factor. Consequently, this inhibits the absorption of vitamin B12. [10]

An overload of Gram-negative bacteria (e.g. E. coli) in the small intestine also hinders the function of the intrinsic factor.

Moreover, an infection of parasites with lamblia reduces the binding of the intrinsic factor to specific receptors in the small intestine.

Experiments on mice have shown that a lack of intrinsic factor leads to a higher susceptibility to certain infections. For instance,  salmonella or citrobacter (enterobacteria).

All in all, this scientific evidence assumes that the intrinsic factor has one or more unknown roles in bacterial and parasitic infections.

Vitamina B12 e infecciones


Above all, the intrinsic factor plays a key role in the absorption of vitamin B12 through the small intestine. In fact, a lack of intrinsic factor or a low production leads to a vitamin B12 deficiency. Then, we can only treat with a high daily dose of vitamin B12 (1.000 mcg to 2.000 mcg per day), either orally or by injection.

Vitamin B12, the malabsorption syndrome, and cobalamin

Cobalamin is the technical term for vitamin B12. The main cause of a vitamin B12 deficiency is a malabsorption syndrome.

This disease usually happens when the stomach lining loses its ability to produce the intrinsic factor. As you already know, this is the protein that binds to vitamin B12 and allows the body to absorb it in the small intestine.

Vitamin B12 and a gastric acid deficiency in the stomach

Indigestion and esophagitis due to reflux usually occur when the stomach produces too much acid. However,  it is also due to the opposite casein most cases. In other words, it is due to the fact that the stomach produces very little gastric acid.

This gets even worse because many people with indigestion and heartburn take acid-blocking medicines. In fact, they inhibit the stomach ability to produce the hydrochloric acid that the body needs.

Moreover, a lack of acidity in the stomach makes the digestion more difficult and reduces the amount of nutrients that the organism absorbs.

A lack of gastric acid in the stomach prevents the intrinsic factor from absorbing vitamin B12. This is one of the reasons why many people have a severe B12 deficiency.
If you want, you can buy Vitamin B12 supplements at the HSN online store.

Studies and References:

  1. Neale G. B12 Proteínas de unión Good, 1990, 31, 59-63.
  2. Se arregló HP. La secreción del factor intrínseco y la absorción de la cobalamina. Fisiología y fisiopatología en el tracto gastrointestinal. Scand J Gastroenterol Suppl. 1991; 188: 1-7.
  3. Kapadia CR. Vitamina B12 en la salud y la enfermedad: Parte I – Trastornos hereditarios de la función, absorción y transporte. Gastroenterólogo. 1995 Dic; 3 (4): 329-44.
  4. Boina Abdallah A, Ogier de Baulny H, Kozyraki R. ¿Cómo se pueden espaciar las inyecciones de cobalamina en la terapia a largo plazo para los errores congénitos de la absorción de la vitamina B (12)? Mol Genet Metab. 2012 Sep; 107 (1-2): 66-71.
  5. Berlin H, Berlin R, Brante G. Oral Tratamiento de la anemia perniciosa con altas dosis de vitamina B12 sin factor intrínseco. Acta Med Scand. 1968 Oct; 184 (4): 247-58.
  6. Vidal Alaball J, Butler C, Cannings-John R, y col. Vitamina B12 oral versus vitamina B12 intramuscular para tratar la deficiencia de vitamina B12. Cochrane Database Syst Rev. 2005; (3): CD004655.
  7. Ankar A, Bhimji S. Vitamina, B12 (cobalamina), Deficiencia. [Actualizado el 20 de junio de 2017]. En: StatPearls [Internet]. Treasure Island (FL): Publicación de StatPearls; 2017 Jun
  8. Bunting RW, Bitzer AM, Kenney RM. Prevalencia de anticuerpos de factor intrínseco y malabsorción de vitamina B12 en pacientes ingresados ​​en un hospital de rehabilitación. J Am Geriatr Soc. 1990 Jul; 38 (7): 743-7.
  9. Herzlich BC, Schiano TD, Moussa Z. Disminución de la secreción del factor intrínseco en el SIDA: relación con la capacidad secretora del ácido parietal y la malabsorción de vitamina B12. En el J gastroenterol. 1992 Dec; 87 (12): 1781-8.
  10. Ayesh MH, Jadalah K, Al Awadi E. Asociación entre las células de nivel de vitamina B12 y anti-parietales y anticuerpos anti-factor intrínseco. Braz J Infect Dis. 2013 nov-dic; 17 (6): 629-32.

Related entries:

Intrinsic Factor Review

Lack of Intrinsic Factor - 100%

Onset of Infections - 100%

Gastric Acid Deficiency - 100%

Efficacy - 100%


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About Carlos Sánchez
Carlos Sánchez
Carlos Sánchez has a degree in Human Nutrition and Dietetics, and therefore all his actions are rigorously backed by science.
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