Homocysteine, Inflammation, and Oxidative Stress: Reassessing a Controversial Biomarker in Cardiovascular Diseases

Abstract

Homocysteine, a sulfur-containing amino acid, has long been studied as a potential risk factor for cardiovascular disease. While initial studies found strong correlations between elevated serum homocysteine concentrations and cardiovascular events, interventional trials aimed at reducing its levels through B-vitamin supplementation failed to demonstrate improved outcomes. In this review, we highlight the experimental studies demonstrating homocysteine’s effects on oxidative stress, immune activation, and endothelial dysfunction, all of which are key contributors to atherogenesis. We also emphasize homocysteine’s interactions with other risk factors and its reinterpretation as a biomarker of vascular diseases rather than a direct therapeutic target. Thus, evidence on the impact of anti-inflammatory and antioxidant strategies on homocysteine-related pathways is also explored. In this manner, we suggest that homocysteine’s clinical utility lies in its ability to signal underlying inflammatory and oxidative stress. Future research should prioritize modulation of downstream oxidative and inflammatory pathways rather than isolated homocysteine reduction.