Vitamin B12 / Folate

Vitamin B12 (cobalamin) and folate (vitamin B9) are essential coenzymes in one-carbon metabolism: B12 is required for methionine synthase (which regenerates methionine from homocysteine) and methylmalonyl-CoA mutase, while folate supplies methyl groups via the folate cycle. Deficiency of either causes megaloblastic anemia by impairing DNA synthesis; B12 deficiency additionally produces neurological damage — including subacute combined degeneration of the spinal cord — through mechanisms not fully replicated by folate. Low B12 is prevalent in older adults, strict vegans, and those taking metformin or proton pump inhibitors. Functional B12 status is more accurately reflected by elevated methylmalonic acid and holotranscobalamin (active-B12) than by total serum B12 alone, which can be misleadingly normal. Both markers are clinically used to investigate elevated homocysteine and associated cardiovascular and cognitive risk.