The homocysteine paradox.

There is little doubt that elevation of plasma total homocysteine is associated with increased cardiovascular risk. Over the past 2 decades, many large prospective studies have established that hyperhomocysteinemia predicts for an increased relative risk of coronary events, stroke, venous thromboembolism, and death.1,2 Hyperhomocysteinemia also has been shown to produce abnormalities of vascular structure and function in animal models.3 Paradoxically, however, several intervention trials have failed to demonstrate any clinical benefit from homocysteine-lowering therapy.4 – 8 What is the explanation for this paradox?