Homocysteine is a sulfur-containing amino acid found in plasma. In the late 1960s a connection between homocysteine and cardiovascular disease was proposed when it was observed that people with a rare hereditary condition called homocystinuria are prone to develop severe cardiovascular disease in their teens and twenties. In this condition, an enzyme deficiency causes the amino acid homocysteine to accumulate in the serum (and be excreted in the urine). Abnormally high homocysteine levels also occur in people whose diet contains inadequate amounts of folic acid, vitamin B6, or vitamin B12.
Studies done in the 1980s and 1990s linked elevated blood levels of homocysteine to increased risk of premature coronary artery disease, stroke, and venous blood clots, even among people with normal cholesterol levels. These studies lead the way to marketing serum homocysteine as a novel biomarker for cardiovascular risk and disease (much like hsCRP). The volume of homocysteine testing increased rapidly and many labs started offering the test. However, while it is true that lowering the serum concentration of homocysteine has been proven to reduce the risk of adverse cardiovascular events among people with homocystinuria, it was not known whether abnormal homocysteine levels among the general population actually cause atherosclerosis. Since then, large controlled studies have found that treatment with B-vitamins does not reduce the incidence of cardiovascular events despite significant lowering of homocysteine levels. In fact, a 7-year study of women with kidney disease secondary to diabetes found that those who took a B-vitamin supplement actually had more heart attacks and strokes than those who did not.
We are now fairly certain that taking B-vitamins to lower homocysteine levels will not lower the incidence or heart attacks or strokes, except for people with homocystinurea. So although homocysteine measurement has value in working up patients with vitamin deficiencies or actual homocystinurea, it is no longer recommended for routinely screening patients to assess their cardiovascular risk.
