ReviewVitamin B12: For more than just the treatment of megaloblastic anemia?Vitamina B12: ¿para algo más que el tratamiento de la anemia megaloblástica?
Introduction
Vitamin B12, or cobalamin, belongs to the group of water-soluble vitamins that play a role in myelin formation, red blood cell maturation, and nucleic acid synthesis. It is synthesized exclusively by bacteria and is obtained through the intake of foods derived from animals, such as eggs, milk and dairy products, red meat and poultry, liver (mainly beef liver), fish, and seafood, among other sources. Our gut microbiota is insufficient for producing the vitamin B12 necessary to meet daily needs, which vary according to age and condition. In general, the daily recommended intake is 2.4 μg/day for adults 2.8 μg/day during pregnancy and breastfeeding.
In order for it to be absorbed during digestion, there must be hydrochloric acid and pepsin that break down proteins in the diet, thus releasing the cobalamin, and a protein called intrinsic factor (IF), which binds to it forming the IF + B12 complex. This protects it until the terminal ileum, where it passes into the blood through active transport after binding to cubam receptors located in the membrane of enterocytes. Only 1% is absorbed through passive diffusion (Fig. 1). It arrives to the liver through the portal system bound to holotranscobalamin, transforming into its two biologically active forms: methylcobalamin and 5′-deoxyadenosylcobalamin, a part of which is stored in the hepatocyte as adenosylcobalamin.
Liver cobalamin reserves allow for several years of little or no vitamin B12 intake before signs of vitamin B12 deficiency appear. In systemic circulation, cobalamin is bound to transcobalamin II and disseminates through tissues, including the central nervous system. It passes to the cell interior through endocytosis through CD320 receptors.
Vitamin B12 is mainly excreted through the biliary tract via enterohepatic circulation, through which a part is reabsorbed and another is eliminated (30%–60% of daily oral intake) in the feces. The amount of B12 left over after its distribution through the body—a small percentage—is eliminated through the renal pathway.
Its clinical indication is for the treatment of hypovitaminosis B12. It is administered orally or intramuscularly in the form of hydroxocobalamin (Megamilbedoce® which contains 10,000 μg of hydroxocobalamin in 2-mL ampoules) or cyanocobalamin (Optovite B12® which contains 1000 μg of cyanocobalamin in 2-mL ampoules). The two available presentations are stable and water-soluble. They are mainly administered intramuscularly and orally when no diseases or conditions which decrease its enteral absorption are present. According to the technical datasheets of both presentations, intravenous administration is not recommended (except in the case of extreme thrombocytopenia, according to both datasheets) due to the risk of anaphylaxis.
To date, no vitamin B12 toxicity has been described except for allergy to the cobalt present in the molecule, the prevalence of which in Spain is estimated to be 10.8% of all patients who visit a skin allergy unit1. It is a type IV allergy mediated by T-CD4 lymphocytes.
The range of vitamin B12 concentration in the blood considered normal is between 150 and 900 pg/mL, approximately, depending on the particular laboratory. Two clinical conditions may occur: one caused by a cobalamin deficit (≤150 pg/mL)2 which is the most commonly and best studied, and one caused by an excess of vitamin B12 (>900 pg/mL).
Currently, the determination of serum vitamin B12 levels are routinely measured in our setting using automatized immunochemiluminescence methods that are widely used due to their speed, economy, and reliability2.
Section snippets
Hypovitaminosis B12
Hypovitaminosis B12 is the most known and studied form of vitamin B12 level abnormalities. It mainly occurs due to a deficit in dietary intake, such as in malnutrition, vegetarian or vegan individuals, older adults, pregnant individuals, or individuals with alcohol use disorder; in ailments in which its intestinal absorption is decreased, such as in atrophic gastritis, intestinal malabsorption syndrome, and gastrointestinal surgery; associated with the intake of certain drugs, such as antacids,
Hypervitaminosis B12
Until now, hypervitaminosis B12 has been perceived as an incidental laboratory finding, scarcely studied if compared to hypovitaminosis B12 and going unnoticed most of the time. However, it has recently sparked greater interest in clinical practice. Indeed, a higher prevalence of excess cobalaminemia compared to a deficit has been described (18.5% vs. 2.2%), as was found in a recent single-center French study19 with 411 vitamin B12 determinations among patients hospitalized in the internal
Funding
This work has not received any type of funding.
Conflicts of interest
The authors declare that they do not have any conflicts of interest.
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