Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for cobalamin (vitamin B12). The Panel considers that the approach based on a combination of biomarkers of cobalamin status, i.e. serum cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA) and plasma total homocysteine (tHcy), is the most suitable approach to derive DRVs for cobalamin. The Panel notes the uncertainties with respect to cut-off values for cobalamin insufficiency of these indicators and that an Average Requirement (AR) cannot be determined from the limited data available. There is consistent evidence in adults that a cobalamin intake of 4 µg/day and greater is associated with serum concentrations of holoTC and cobalamin within the reference ranges derived from healthy subjects, together with MMA and tHcy concentrations below the cut-off values for adults, which indicates an adequate cobalamin status. Therefore, the Panel sets an Adequate Intake (AI) for cobalamin at 4 µg/day for adults based on data on different biomarkers of cobalamin status and in consideration of observed mean intakes, which range between 4.2 and 8.6 μg/day in adults in several EU countries. AIs for infants and children are calculated by extrapolation from the AI for adults using allometric scaling and applying a growth factor. Estimated AIs range from 1.5 µg/day in infants aged 7-11 months to 4 µg/day in children aged 15-17 years. For pregnancy and lactation, additional cobalamin intakes related to the accumulation of cobalamin in fetal tissues and transfer of cobalamin into breast milk are considered and AIs of 4.5 and 5 µg/day, respectively, are proposed. 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 succinylCoA 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.
© EuropeanCobalamin absorption consists of several steps, including its release from proteins, its binding by gastric intrinsic factor and the absorption of intrinsic factor-cobalamin complexes through receptormediated endocytosis in the terminal ileum. Fractional absor...