Homocysteine and Cardiovascular Disease: A Narrative Review of Mechanisms, Associations, and Intervention Evidence

Homocysteine is a sulfur-containing intermediate in methionine metabolism whose circulating concentration reflects interactions among nutritional status, enzyme activity, kidney function, and inherited metabolic disorders.Folate and vitamin B12 participate in its remethylation to methionine, while vitamin B6 supports its conversion through the transsulfuration pathway.Elevated homocysteine concentrations have been associated with coronary and cerebrovascular disease, and experimental studies have identified potential mechanisms involving endothelial dysfunction, oxidative stress, inflammatory signaling, and impaired fibrinolysis.However, these associations and experimental observations do not establish that modest elevations directly cause clinical vascular events.Although folic acid-based supplementation lowers homocysteine concentrations, randomized trials have not consistently demonstrated corresponding reductions in cardiovascular events.Evidence of benefit is more favorable for stroke prevention in certain populations than for coronary outcomes.This narrative review examines homocysteine metabolism, proposed vascular mechanisms, observational associations, and intervention findings, emphasizing the distinction between biochemical improvement and clinical benefit.Homocysteine measurement and treatment should be interpreted according to a specific clinical indication, particularly suspected nutritional deficiency or inherited metabolic disease, rather than an elevated concentration alone.