Serum B12 measures total cobalamin. B12 is essential for DNA synthesis, red blood cell maturation, and myelin production. Deficiency causes megaloblastic anaemia and subacute combined degeneration of the spinal cord with irreversible neurological damage.

Serum B12 can appear normal in functional deficiency. Active B12 (holotranscobalamin) and functional markers (MMA, homocysteine) provide more sensitive assessment. Testing is particularly important in vegans, older adults, and those on metformin or PPIs.