Homocysteine
A sulfur amino acid intermediate in methionine metabolism, raised by B12, folate or B6 deficiency and by polymorphisms such as MTHFR. It was proposed to promote endothelial dysfunction and thrombosis, and it is strongly and consistently associated with cardiovascular events across observational cohorts. It has since become the standard cautionary tale about exactly how much that kind of association is worth.
Lonn E, Yusuf S, Arnold MJ, et al. (HOPE-2) “Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease.” N Engl J Med 2006;354:1567–1577 lowered homocysteine by roughly 25% in 5,522 high-risk patients using folic acid with B6 and B12, and did not reduce major cardiovascular events overall — a stroke reduction appeared, but not for MI or cardiovascular death. Later Mendelian randomisation data are similarly unsupportive of a direct causal cardiovascular role. The test remains clinically useful inside a B12 or folate deficiency workup.
Lonn E, et al. N Engl J Med. 2006. PubMed: PMID 16531613