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The Mechanism of Absorption of Vitamin B12 (cobalamin) in the GI Tract

Summary:

  • Vitamin B12 is a well known water soluble vitamin necessary for a number of metabolic reactions and prevention of medical complications, most commonly hematopoietic disorders and spinal cord related neuropathies.
  • If vitamin B12 is ingested in its free (or nonprotein bound form), it will bind to a carrier protein known as R-binders or transcobalamin I that is secreted by both the salivary glands in the oropharynx and the gastric mucosal cells within the stomach.
  • If the vitamin B12 is ingested in its protein bound form, it must first undergo a proteolytic cleavage in the stomach or duodenum where it will bind to an R-binder and enter into the duodenum for further cleavage.
  • Upon entry into the second segment of the duodenum, the pancreas will secrete additional protease which will then degrade the R-binders holding onto the vitamin B12.  It is at this point that vitamin B12 will bind to or complex with intrinsic factor for the remainder of its journey to the ileum of the small intestine for absorption.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Reviewer:
Jon D. Herrington, PharmD, BCPS, BCOP
Last Reviewed: August 2015

Explanation

  • Vitamin B12 is a well known water soluble vitamin necessary for a number of metabolic reactions and prevention of certain medical complications, most commonly hematopoietic disorders and spinal cord related neuropathies (additional details to these disorders will be summarized in future publications).1,2  Vitamin B12 is also known as cobalamin or cyanocobalamin (the form found in most over the counter supplements).1  It gets its name in part due to its chemical structure since it contains cobalt, thus the reason it is known as cobalamin.1  As with any vitamin, human beings cannot synthesize or produce their own vitamins and thus must obtain them from dietary sources, bacteria making up our normal flora, and/or through supplements.  As such, vitamins are "vital to life". 

    As it relates to the need for vitamin B12, the molecular state in which the vitamin B12 is introduced into the body can impact how efficient it can be absorbed from a normally functioning gastrointestinal tract.  Vitamin B12 bound to protein in foods must undergo an initial or early separation reaction before it can be absorbed in the ileum of the small intestine, whereas most forms found in supplements do not undergo this separation reaction as they are already in the free form.  Recognizing this difference becomes important in future publications related to drug interactions and their clinical context.  For now, the following concisely describes the sequence of events that must take place for vitamin B12 to get into the body.

    If vitamin B12 is ingested in its free (or nonprotein bound form), it will bind to a carrier protein known as R-binders or transcobalamin I that is secreted by both the salivary glands in the oropharynx and the gastric mucosal cells within the stomach (see figure 1 below).1,2  The free vitamin B12 ingested by mouth will remain in the bound form with an R-binder until it reaches the second segment of the duodenum in the small intestine. 

                              

    If the vitamin B12 is ingested in its protein bound form, then it must first undergo a proteolytic cleavage in the stomach or duodenum where it will bind to an R-binder and then enter into the duodenum for further cleavage.1,2  This proteolytic cleavage is mostly dependent on the functional activity of pepsin.  As a reminder, the chief cells within the stomach will secrete the pepsinogen into the lumen of the stomach.  The presence of the hydrochloric acid also provided by the parietal cells is necessary to convert the pepsinogen to pepsin.  The functionally active pepsin can then degrade the newly ingested protein source holding onto to the vitamin B12.  Upon this protein degradation, the free vitamin B12 will then proceed as above to be bound to an R-binder or transcobalamin I for entry into the duodenum.  Therefore, regardless of the molecular state of vitamin B12 ingested, it is mostly delivered to the duodenum as a complex with an R-binder. 

    Intrinsic factor is also present in the gastric and intestinal contents that contain the vitamin B12 complexed to R-binders and being delivered to the duodenum.  In addition to the hydrochloric acid secreted from the stomach, the properly functioning parietal cells also secrete intrinsic factor, however nothing is bound to the intrinsic factor at this point.  Upon entry into the second segment of the duodenum, the pancreas will secrete additional protease, which will then degrade the R-binders holding onto the vitamin B12.  It is at this point the vitamin B12 will bind to (or complex with) intrinsic factor for the remainder of its journey to the ileum of the small intestine for absorption. 

    Assuming a functionally intact ileum, the vitamin B12/intrinsic factor complex is taken up into the enterocyte at this point in the small intestine.  The absorbed vitamin B12 then binds to transcobalamin II where approximately 50% of the vitamin B12 will be delivered to the liver and the remainder will be delivered to other tissues.  In fact, the liver's storage of vitamin B12 is significant enough that it could take a year or more before deficiency of vitamin B12 manifests into clinically relevant pathology.

    References:

    1. Lieberman M, Marks AD.  Tetrahydrofolate, Vitamin B12, and S-adenosylmethionine.  Lieberman M, Marks AD. Eds. In: Mark's Basic Medical Biochemistry: A Clinical Approach.  3rd Ed.  Wolters Kluwer/Lippincott Willaims & Wilkins.  Philadelphia, PA.  2009.
    2. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press, 1998.

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MESH Terms & Keywords

  • Vitamin B12 Absorption, Cobalamin, Cyanocobalamin, Gastrointestinal Tract, Intrinsic Factor