Vitamin B12 is essential for DNA synthesis and for cellular energy production. A vitamin B12 deficiency is common, especially when dietary intake of animal foods is limited or from malabsorption of the vitamin. Vegetarians are at risk of vitamin B12 deficiency as are other groups with low intakes of animal foods or those with restrictive dietary patterns.
Malabsorption of vitamin B12 is most commonly seen in the elderly, secondary to gastric achlorhydria. The symptoms of sub-clinical deficiency are subtle and often not recognized. The long-term consequences of sub-clinical deficiency are not fully known but may include adverse effects on pregnancy outcomes, vascular, cognitive, bone and eye health.
Also known as cobalamin, B12 comprises a number of forms including cyano-, methyl-, deoxyadenosyl- and hydroxy-cobalamin. The cyano form, which is used in supplements, is found in trace amounts in food . The other forms of cobalamin can be converted to the methyl- or 5-deoxyadenosyl forms that are required as co factors for methionine synthase and L-methyl-malonyl-CoA mutase.
Methionine synthase is essential for the synthesis of purines and pyrimidines. The reaction depends on methyl cobalamin as a co-factor and is also dependent on folate, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to form methionine and tetrahydrofolate. A deficiency of vitamin B12 and the interruption of this reaction leads to the development of megaloblastic anaemia.
Folate deficiency independent of vitamin B12 also causes megaloblastic anaemia. Methylmalonyl CoA mutase converts methylmalonyl CoA to succinyl CoA, with 5-deoxy adenosyl cobalamin required as a cofactor. It is a defect in this reaction, and the subsequent accumulation of methylmalonyl CoA that is thought to be responsible for the neurological effects in vitamin B12 deficiency.