This article, part of the "STEPed Care" series, explores the relationship between homocysteine levels and cardiovascular disease (CVD). Homocysteine is an amino acid that can lead to endothelial injury, free radical damage, and other factors contributing to atherosclerosis. Elevated homocysteine levels have been established as an independent risk factor for CVD, including coronary heart disease (CHD), peripheral vascular disease, stroke, and venous thrombosis. The article reviews several studies that support this association, noting that homocysteine concentrations above 15 μmol/L are most consistently linked with increased CVD risk. Folic acid is highlighted as the most effective agent for lowering homocysteine levels, with doses below 2 mg generally considered safe. The US Public Health Service recommends 400 μg of folic acid daily for women of childbearing potential to prevent neural tube defects. However, dietary intake of folic acid is often insufficient, and fortification of grain products with folic acid has been mandated by the FDA. The article also discusses the safety and tolerability of folic acid supplementation, noting that it is generally well-tolerated, with potential toxicities being dose-dependent. The effectiveness of folic acid in reducing homocysteine levels and CVD risk is supported by several studies, although randomized controlled trials are lacking. The cost of folic acid is extremely low, making it a potentially beneficial intervention for preventing and managing CVD. In conclusion, while the exact threshold for increased CVD risk and the optimal dose of folic acid remain unclear, the potential benefits of folic acid supplementation outweigh the risks. The article recommends widespread use of folic acid supplementation, particularly in patients with documented CHD or cardiovascular risk factors.This article, part of the "STEPed Care" series, explores the relationship between homocysteine levels and cardiovascular disease (CVD). Homocysteine is an amino acid that can lead to endothelial injury, free radical damage, and other factors contributing to atherosclerosis. Elevated homocysteine levels have been established as an independent risk factor for CVD, including coronary heart disease (CHD), peripheral vascular disease, stroke, and venous thrombosis. The article reviews several studies that support this association, noting that homocysteine concentrations above 15 μmol/L are most consistently linked with increased CVD risk. Folic acid is highlighted as the most effective agent for lowering homocysteine levels, with doses below 2 mg generally considered safe. The US Public Health Service recommends 400 μg of folic acid daily for women of childbearing potential to prevent neural tube defects. However, dietary intake of folic acid is often insufficient, and fortification of grain products with folic acid has been mandated by the FDA. The article also discusses the safety and tolerability of folic acid supplementation, noting that it is generally well-tolerated, with potential toxicities being dose-dependent. The effectiveness of folic acid in reducing homocysteine levels and CVD risk is supported by several studies, although randomized controlled trials are lacking. The cost of folic acid is extremely low, making it a potentially beneficial intervention for preventing and managing CVD. In conclusion, while the exact threshold for increased CVD risk and the optimal dose of folic acid remain unclear, the potential benefits of folic acid supplementation outweigh the risks. The article recommends widespread use of folic acid supplementation, particularly in patients with documented CHD or cardiovascular risk factors.