Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a Scientific Opinion on Dietary Reference Values for the European population, including cobalamin (vitamin B12).
Cobalamin is a metal complex with a central cobalt atom bonded to six ligands. The upper or β-axial ligand varies (R-group: cyano-, hydroxo-, aquo-, methyl- or adenosyl-group), giving rise to the correspondingly named chemical forms of the vitamin. In humans, two reactions are known to require cobalamin as coenzyme. One is the rearrangement of methylmalonyl-coenzyme A (CoA) to succinyl-CoA in propionate metabolism by methylmalonyl-CoA mutase in mitochondria. The other is the cytosolic transmethylation of homocysteine by 5-methyl-tetrahydrofolate to methionine by methionine synthase. The most frequent clinical expression of cobalamin deficiency is megaloblastic anaemia. Independent of megaloblastic anaemia, neurological dysfunction is another clinical feature of cobalamin deficiency. Cobalamin insufficiency is characterised by biochemical abnormalities, such as elevated total homocysteine (tHcy) and/or methylmalonic acid (MMA) concentrations in blood resulting from impaired cobalamin metabolic activity, with no specific clinical symptoms.