Vitamin B12 Deficiency



Vitamin B12 absorption

The primary function of the small intestine is the absorption of nutrients, minerals and vitamins released from food through the process of digestion. This presents a paradox to the intestine, which is specifically designed to stop molecules released from pathogens such as viruses, bacteria and parasites from crossing into the circulation. Initially it was thought that the process of absorption was highly non-specific such that all molecules simply diffused through the cells that line the small intestine and from there enter the circulation. More recently it has been discovered that the process of absorption is a highly specific process that requires specific pores and transporters to enable more specific uptake of molecules such as water soluble vitamins, fats, fat soluble vitamins, minerals, amino acids, sugars and there are even pores involved in uptake of water (aquaporins). Even small sugar molecules such as hexose and glucose are transported via the sodium-glucose transporters. There are transporters for individual amino acids, for dipeptides and nucleotides, as well as organic cation transporters, organic anion transporters, bile acid transporters and fatty acid transporters, and there are even transporters for small atoms such as copper. Basically there appear to be some sort of transporter for all small dietary molecules (1).


That is fine for very small molecules, but what about larger molecules such as the larger water soluble vitamins (folate, biotin, riboflavin and vitamin B12) and proteins such as insulin, IGF1, lactoferrin, and even very large proteins such as antibody molecules, how do they get across the gut? It turns out that this problem is not unique to the gut, but also occurs in the alveolar epithelium, the vascular endothelium, the renal proximal tubular endothelium and the blood brain barrier.


It is apparent, though that very large molecules do in fact cross the intestinal cells as can be attested to by allergic reactions to dietary allergens and the response to many diarrhea-causing gut pathogens. It has been established that entry of these larger molecules requires that they either bind to, or are bound by some sort of recognition molecule on the intestinal wall. Generally this is a receptor that is specific for the molecule. Once the receptor has bound to the molecule to be taken into the cell, the cell envelopes the molecule in a process called endocytosis and then subsequently transports the molecule across the gut.




Transport in the small intestine

1. Russell-Jones GJ Intestinal receptor targeting for peptide delivery: reasons for failure and new opportunities (Avail on request)

2. Russell-Jones, G. J. and Aizpurua, H. J. de. 1987 Mucosal Immunogens In: Recent Advances in Mucosal Immunology,. Ed. J. Mestecky, J. R. McGhee, J. Bienenstock and P. L. Ogra. (Plenum Publishing Co, New York and London) Adv. Exp. Med. Biol., 216B, 1791-1799.

2. de Aizpurua, H. J. and G. J. Russell-Jones 1987 Oral vaccination: Identification of classes of proteins which provoke an immune response upon oral feeding. J. Exp. Med. 167 : 440-451

3. Bergmann et al 1989 Adjuvant effect of B-subunit of E. coli heat labile toxin on secretory antibody response to oral influenza virus immunization in mice. Allergologie. 12 : 294.

4. Bergman et al 1991 B Subunit of E. Coli heat-labile enterotoxin enhances secretory IgA antibody response to oral influenza virus immunization in mice. Schweizerische Medizinische Wochenschrift. 121 : Suppl 40/II, 28.

5. Stewart et al 1992 Immunization using recombinant TraT-LHRH fusion proteins. Vaccines 92, 51-55 (Cold Spring Harbor Laboratory Press).

6. Russell-Jones, G.J. 1993 Oral Vaccination with Lectins and Lectin-Like Molecules. In "Novel Delivery Systems for Oral Vaccine Development" Ed. Derek O'Hagan, CRC Press pp 296-299.

7. Russell-Jones, G.J. 1993 Oral delivery systems for proteins and peptides: The use of lectins for oral immunization and the use of the VB12-uptake system for the delivery of peptide and protein pharmaceuticals. Proceed. of "Business Opportunities in Peptide and Protein Delivery". Leiden, Netherlands

8. Lazorová,et al 1993. Intestinal tissue distribution and epithelial transport of the oral immunogen LTB, the B subunit of E. coli heat-labile enterotoxin. J. Drug Targeting 1, 331-40

9. Lindner et al 1994 Identification of the site of uptake of the E. coli Heat-Labile enterotoxin, LTB. Scand. J. Immunol. 40, 564-572.

10. Russell-Jones, G. J. 1996 The potential use of receptor-mediated endocytosis for oral drug delivery. In “Carrier mediated approaches for oral drug delivery” Advanced Drug Delivery Reviews, 20, 83-96. Eds. Øie, S., Szoka, F. C., and Swaan, P. W.

11. Russell-Jones, G. J. 1999 Carrier-mediated transport for oral drug delivery. Encyclopedia of Controlled Drug Delivery Ed. E. Mathiowitz

12. Russell-Jones G. J. 1999 Use of bioconjugates for oral delivery of peptides, proteins and immunogens. In “Drug Delivery Science and Technology”. STP Pharma Sciences Janvier-Fevrier.

13. Alsenz et al 2000 Oral absorption of peptides through the cobalamin (vitamin B12) pathway in the rat intestine. Pharm Res. 2000 Jul;17(7):825-32. PMID: 10990201 [PubMed - indexed for MEDLINE]

14. Russell-Jones, G. J. 2000 Oral vaccine delivery. J. Control. Rel., 65, 49-54.

15. Russell-Jones, G. J. 2001 The potential use of receptor-mediated endocytosis for oral drug delivery. In “Carrier mediated approaches for oral drug delivery” Advanced Drug Delivery Reviews, 46, 59-73. (Special commemorative edition. Eds. Øie, S., Szoka, F. C., and Swaan, P. W.).

16. Russell-Jones, G.J. 1995 Oral delivery of Therapeutic Proteins and peptides by the vitamin B12 uptake system. In "Peptide-based Drug Design: Controlling Transport and Metabolism." Ed. M. Taylor and G. Amidon, ACS Publications pp181-198.

17. Russell-Jones, G.J. 1994 Oral delivery of Therapeutic Proteins and Peptides by the Vitamin B12 Uptake System. In "Pharmaceutical Manufacturing International" Ed P Barnacal.

18. Russell-Jones and Aizpurua. 1988 Vitamin B12: A novel carrier for orally presented antigens. Proceed. Int. Symp. Control. Rel. Bioact. Mater. 15 : 142-143.

19. Russell-Jones and Alpers 1998 Vitamin B12 transporters. In “Membrane transporters as drug targets” Pharmaceutical Biotechnology Vol. 12 Ed. W. Sadeé and G. Amidon. Plenum press. (Review).

20. Russell-Jones, G. J. 1998 Use of Vitamin B12 conjugates to deliver protein drugs by the oral route. Critical Reviews in Therapeutic Drug Carrier Systems, 16, 557-558. (Review)

21. Russell-Jones, G. J. 2004 Use of targeting agents to increase uptake and localization of drugs to the intestinal epithelium. J. Drug Targ, 12, 113-23 (Review)

22. Russell-Jones et al 1995. Vitamin B12 mediated oral delivery systems for Granulocyte Colony Stimulating Factor and Erythropoietin. Bioconjugate Chemistry, 6, 459-465

23. Habberfieldet al 1996. Vitamin B12-mediated uptake of erythropoietin and granulocyte colony stimulating factor in vitro and in vivo. Int. J. Pharmacol., 145, 1-8

24. Russell-Jones, G. J. (1996) Utilisation of the Natural Mechanism for Vitamin B12 uptake for the oral delivery of therapeutics. Eur. J. Pharm. Biopharm. 42, 241-249.

25. Habberfield et al 1996 Vitamin VB12-mediated uptake of recombinant therapeutic proteins from the gut. Int. J. Pharm., 145, 1-8.

26. Russell-Jones G. J. 2000 Use of the vitamin B12 transport system to enhance the oral bioavailability of peptides and proteins. In “Drug Targeting in the Gastrointestinal Tract” Ed. Josef Tukker. Harwood Academic Publishers.


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The statements on this site compose a compendium of generally recognized signs of vitamin B12 deficiency, and problems that can then ensue They also are formulated from a summary of relevant scientific publications. In addition they may contain some forward looking statements of a general nature.
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