Chemical structure of Vitamin B12
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Vitamin B12 Deficiency

The term vitamin B12 (or B12 for short) is used in two different ways. In a broader sense it refers to a group of Co-containing compounds known as cobalamins - cyanocobalamin (an artefact formed as a result of the use of cyanide in the purification procedures), hydroxocobalamin and the two coenzyme forms of B12, methylcobalamin (MeB12) and 5-deoxyadenosylcobalamin (adenosylcobalamin - AdoB12). more...

VACTERL association
Van der Woude syndrome
Van Goethem syndrome
Varicella Zoster
Variegate porphyria
Vasovagal syncope
VATER association
Velocardiofacial syndrome
Ventricular septal defect
Viral hemorrhagic fever
Vitamin B12 Deficiency
VLCAD deficiency
Von Gierke disease
Von Hippel-Lindau disease
Von Recklinghausen disease
Von Willebrand disease

In a more specific way, the term B12 is used to refer to only one of these forms, cyanocobalamin, which is the principal B12 form used for foods and in nutritional supplements.

Pseudo-B12 refers to B12-like substances which are found in certain organisms, such as Spirulina spp. (blue-green algae, cyanobacteria). However, these substances do not have B12 biological activity for humans.


B12 is the most chemically complex of all the vitamins. B12's structure is based on a corrin ring, which, although similar to the porphyrin ring found in haem, chlorophyll, and cytochrome, has two of the pyrrole rings directly bonded. The central metal ion is Co (cobalt). Four of the six coordinations are provided by the corrin ring nitrogens, and a fifth by a dimethylbenzimidazole group. The sixth coordination partner varies, being a cyano group (-CN), a hydroxyl group (-OH), a methyl group (-CH₃) or a 5'-deoxyadenosyl group (here the C5' atom of the deoxyribose forms the covalent bond with Co), respectively, to yield the four B12 forms mentioned above. The covalent C-Co bond is the only carbon-metal bond known in biology. (p.32)


B12 cannot be made by plants or by animals, as the only type of organism that have the enzymes required for the synthesis of B12 are bacteria (eubacteria, archaebacteria).


Coenzyme B12's reactive C-Co bond participates in two types of enzyme-catalyzed reactions: (p.675)

  1. Rearrangements in which a hydrogen atom is directly transferred between two adjacent atoms with concomitant exchange of the second substituent, X, which may be a carbon atom with substituents, an oxygen atom of an alcochol, or an amine.
  2. Methyl (-CH₃) group transfers between two molecules.

In humans there are only two coenzyme B12-dependent enzymes:

  1. MUT which uses the AdoB12 form and reaction type 1 to catalyze a carbon skeleton rearrangement (the X group is -COSCoA). MUT's reaction converts MMl-CoA to Su-CoA, an important step in the extraction of energy from proteins and fats (for more see MUT's reaction mechanism)
  2. MTR, a methyl transfer enzyme, which uses the MeB12 and reaction type 2 to catalyzes the conversion of the amino acid Hcy into Met (for more see MTR's reaction mechanism).


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Low vitamin B-12 and folic acid fortification - Vitamins and Minerals - masking of vitamin B-12 deficiency - Author Abstract
From Nutrition Research Newsletter, 7/1/03

In some patients with Vitamin B-12 deficiency mistakenly treated with folic acid, anemia resolved but neurologic complications became worse. This phenomenon, known as masking of vitamin B-12 deficiency, has never been studied systematically for the obvious reason that patients would never knowingly be given the wrong treatment, particularly when the neurologic damage associated with vitamin B-12 deficiency is often irreversible. Therefore, little is known about how frequently masking occurs and of the lowest dose of folic acid that produces masking.

Fortification of enriched cereal grains with folic acid has raised concerns that people who consume large quantities of cereal grains, particularly the elderly, may be at increased risk of masking. Therefore, this study was designed to identify patients with low vitamin B-12 before and after most grain products were fortified with folic acid to determine whether the proportion of cases occurring without anemia increased after fortification.

The laboratory results of every patient for whom a vitamin B-12 level was measured at the Veterans Affairs Medical Center in Washington, DC, between 1992 and 2000, were reviewed. Vitamin B-12 concentrations < 258 pmol/L were considered low since this concentration has been shown to correlate well with vitamin B-12 deficiency. Those with a low vitamin B-12 concentrations had their hematocrits and mean cell volumes checked. The proportion without anemia was examined by year before, during and after folic acid fortification began. Fortification was required by January 1, 1998; however, the industry has the option of fortifying anytime after March 5, 1996.

There were 1573 subjects with a low vitamin B-12 concentration. The proportion of subjects without anemia was 39.2% before fortification, 45.5% during the option period of fortification, and 37.6% after fortification was completely implemented. The proportion did not change significantly over the three time periods. These findings did not change when the analysis was limited to patients older than 60 or when a more conservation definition of low vitamin B-12 (< 150 pmol/L) was used.

The findings showed that there was no evidence of an increase in low vitamin B-12 concentrations without anemia. Therefore, the amount of folic acid currently being added to food is not causing a major increase in masking of vitamin B-12 deficiency anemia. Mills et al. acknowledge that the population seeking care at the study facility could have changed over the course of the study. Another limitation was that the subjects were mainly African American and were not a representative sample of the US population. However, the major strengths of the study include the large number of subjects available for investigation and the stable referral pattern. It has also been shown that the actual amount of folic acid being added to food is > 50% more than that called for in the US FDA regulations. Despite this dramatic increase in folic acid, the results again show that food fortification has not caused an increase in vitamin B-12 deficiency masking.

James L Mills, Isabelle Von Kohorn, Mary R Conley, et al., Low Vitamin B-12 Concentrations in patients without anemia: the effect of folio acid fortification of grain, Am J Clin Nutr 77:1474-1477 (dune 2003) [Address reprint requests to JL Mills, Pediatric Epidemiology Section, Division of Epidemiology, Statistics and Prevention Research, 6100 Building, Room 7B03, NICHD, NIH, DHHS, Bethesda, MD 20892. E-mail:]

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