B12 Ankermann Mechanism of Action

Pharmacotherapeutic group: Anti-anaemic, vitamin B12. ATC code: B03BA01.
Pharmacology: Pharmacodynamics: As a member of the prosthetic groups of methylmalonyl CoA isomerase, vitamin B12 is needed to convert propionic acid into succinic acid. Furthermore, alongside folic acid, vitamin B12 is involved in the formation of labile methyl groups which are transmitted to other methyl acceptors via transmethylation processes. The vitamin also influences the synthesis of nucleic acids, in particular during haematopoiesis and other cell maturation processes.
Availability and requirement: The human body is unable to synthesize vitamin B12, and it is absorbed from food. Foods which contain vitamin B12 are liver, kidneys, heart, fish, oysters, milk, egg yolk and meat. Vitamin B12 is administered for therapeutic purposes in the form of cyanocobalamin and/or hydroxocobalamin. Both are pro-drugs that the body converts into the active forms methylcobalamin and 5-adenosylcobalamin. The daily requirement of B12 amounts to around 1 μg.
Signs of deficiency: An impairment or lack of vitamin B12 absorption will eventually result in clinical symptoms if plasma levels fall below 200 pg/ml. The consequences are megaloblastic anaemia and neurological deficits in the peripheral and central nervous system. Polyneuropathy may be present in combination with lesions in the dorsal columns of the spinal cord and psychological disorders. Early signs of deficiency may include fatigue and paleness, tingling in hands and feet, an unsteady gait and reduced physical strength.
Symptoms caused by a vitamin B12 deficiency can only be corrected by the intake of Vitamin B12.
Causes of deficiency: Pernicious anaemia; atrophic gastritis; celiac disease; malabsorption, following partial ventricle resection; as a result of blind-loop syndrome; long-term treatments using active substances which can lead to a reduction in vitamin B12 levels (e.g. gastric acid reducing drugs, aminosalicylates and metformin).
Pharmacokinetics: Vitamin B12 is absorbed via two different routes: Active absorption in the small intestine involving intrinsic factor. The transportation of vitamin B12 into the tissues involves attachment to transcobalamins which are substances from the plasma-beta globulins group.
Independently of intrinsic factor, the vitamin can also pass into the bloodstream by means of passive diffusion via the gastrointestinal tract or the mucous membranes. Approximately 1-3% of orally administered quantities enter the blood in a dose-linear fashion. Thus, for high oral doses (~ 1000 µg/day), adequate absorption is provided even in patients with a lack of intrinsic factor.
Up to 90% of body stores are in the liver, where the vitamin is stored as the active coenzyme with a turnover rate of 0.5 to 0.8 μg daily. In healthy omnivorous adult humans, the total body content of vitamin B12 is about 3 to 5 mg. It will generally take 3-5 years for clinical signs of vitamin B12 deficiency to occur.
Vitamin B12 is excreted mainly by the gall bladder and up to 1 μg is reabsorbed via the enterohepatic circulation. If the body's storage capacity is exceeded due to high doses, in particular subsequent to parenteral administration, the non-retained portion is excreted in the urine.
Toxicology: Preclinical safety data: No toxicity was shown in animal studies even at very high doses. There are no reports of any adverse effects relating to the administration of cyanocobalamin on male and female pre- and postnatal development and no reports of supplement-associated teratogenic, mutagenic or carcinogenic effects.