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Intrinsic Factor (IF) is necessary for the body to absorb B12 naturally. IF protein binds, transports and ensures physiologic B12 absorption by special receptors.

B12-IF image courtesy Prof. Robert Doyle, Syracuse University

stabilizes & transports

B12 is a very large molecule and very vulnerable to being destroyed by stomach acid. IF, which is shaped like a donut, pulls most of the B12 molecule into the 'donut hole' and protects it from destruction. [1]

The IF-B12 complex then travels down approximately 22 feet of intestine to reach the distal ileum where special B12-IF receptors are located.

receptor mediated

B12 is the only nutrient absorbed via specific receptors and this only happens when it is bound to IF. The receptors also absorb only about 3mcg (micrograms) of B12 and daily intake of 4 - 7mcg maintains steady blood levels. [2-5]

This is the body's normal and natural way of absorbing B12, a process that is very precisely controlled because not only is too little B12 a problem, but so is too much. [6,7]

How B12 is absorbed

Sources of IF

Intrinsic Factor is only found in the gastric juices of humans and animals. To obtain enough IF for use clinically, draining the stomachs of humans or other mammals, such as pigs or cattle, was necessary and required purifying huge pooled volumes of specimens.  This method was found to be too difficult and unreliable and is no longer used or regarded as supplying an acceptable source of IF for human use.

Human IF

Human IF was obtained by aspirating and purifying stomach fluid from humans. It became part of the Schilling's test to diagnose Pernicious Anemia, but is no longer available and the test  became obsolete decades ago.

Animal IF

IF has been extracted from gastric and intestinal juices of pigs and cattle and concentrated for use in humans. It is not the same as Human IF and also carries the risk of transmitting diseases like Mad Cow Disease.


Desiccated Stomach Substance is the only animal IF  still on the market and available in a few over-the-counter (OTC) products. It is a crude and unreliable source and is not recommended for people with B12 deficiency.

Xeragenx Intrinsic factor

How Its Made

Protein Synthesis Technology

The technology to program bacterial cells to produce human proteins has been around for decades and has been used by pharmaceutical companies to produce drug products containing injectable proteins like human insulin to treat diabetes. The human genes are inserted into bacteria which are then cultured in huge tanks to produce the human protein and purified - without allergens associated with insulins derived from pigs or cattle (as was the case over 30 years ago).

Plant Factory

Plants are more ideally suited to producing recombinant human Intrinsic Factor (rH-IF) because, unlike animal cells, plants don't have B12-binding proteins to interfere with the purity of IF produced by this technology.

Arabidopsis thaliana or thale cress (a member of the mustard family) was chosen to be the plant factory for IF because it is the most widely studied plant in botany and its genetic code is well understood.

The Arabidopsis plant was 'transformed' with the human IF gene at the University of Aarhus in Denmark and is grown under contract by a world-class plant biosciences company providing scalability for global commercial supply.

Extraction & Purification

Once the plants are harvested, an extraction process is performed that is similar to juicing, or squeezing out every drop of fluid from the plants. This 'green juice' contains human recombinant Intrinsic Factor (rH-IF) as well as many other plant proteins which are removed by a series of purification steps that delivers a highly purified liquid containing human IF.

Intrinsic Factor 3 stages of extraction and purification  shown in 3 separate glass bottles.

Applications for xeragenx human intrinsic factor

Nutritional Supplements

Typical nutritional supplements contain 200 - 400 times the RDI for vitamin B12 and have an absorption rate (bioavailability) of less than 1%. [8] In a study of subjects with severe vitamin B12 deficiency due to the absence of IF, oral B12 alone (9mcg orally every 6 hours) did not increase B12 as measured by a very sensitive blood assay (Holo-TC). However, with the addition of Xeragenx human IF, the B12 level increased by 227% over baseline after a single dose - indicating that high bioavailability of oral B12 was restored to physiologic levels with the addition of human IF.[9]

Other Potential Applications

Pharmaceutical *

IF may offer some protection for proteins from enzymatic degradation in the GI tract. This finding could form the basis for future research into the stability of injectable pharmaceuticals. [10,11]

IF may offer a possible new route for absorption of proteins from the GI tract via the B12-IF receptors in the ileum. [12]

Diagnostic & Imaging *

Xeragenx human IF is purer than 'hog' IF used in current B12 and IF Antibody tests and has the potential to improve sensitivity of these tests.

Isotopically labeled Xeragenx IF was shown to be potentially useful for targeted diagnostic and therapeutic indications in liver [13] and could be applicable to lung.[14]