Vitamin B12, hyperhomocysteinemia, and stroke

Vitamin B12 (cobalamin) is needed for DNA synthesis, so its deficiency causes megaloblastic anemia and other hematological problems, as well as neuropathy, myelopathy, and dementia. It also raises plasma total homocysteine (tHcy), a powerful risk factor for cardiovascular disease. Although “biochemical” B12 deficiency is easily recognized by a serum B12 level below the reference range, “metabolic B12 deficiency” (with inadequate metabolically active B12) is often missed, because measurement of holotranscobalamin, tHcy, or methylmalonic acid is required to detect it. Lowering of homocysteine with B vitamins reduces the risk of stroke, but harm from cyanocobalamin among study participants with renal failure obscures the benefit in early studies. Methylcobalamin or hydroxycobalamin should be used instead of cyanocobalamin, particularly in patients with impaired renal function, including the elderly. Because B12 deficiency is common, has serious consequences, and is easily treated, it should receive more attention.