From the Guidelines
High homocysteine levels are associated with an increased risk of stroke, but current evidence does not support the use of vitamin supplements to lower homocysteine levels for the prevention of stroke or cardiovascular disease in patients with established vascular disease. The clinical implications of high homocysteine levels are significant, as they have been linked to a 19% difference in stroke risk, with a 25% difference in plasma homocysteine concentration corresponding to approximately 3 micromoles per liter 1.
Key Findings
- Hyperhomocysteinemia increases the risk of stroke, with a meta-analysis of 30 studies finding a significant association between elevated homocysteine levels and stroke risk 1.
- The risk of developing extracranial carotid stenosis is increased 2-fold among elderly patients with elevated homocysteine levels 1.
- Folic acid supplementation has been shown to reduce the risk of stroke by 18% in primary prevention trials, but studies in patients with established vascular disease have not confirmed a benefit of homocysteine lowering by B-complex vitamin therapy on cardiovascular outcomes, including stroke 1.
Treatment Implications
- The writing committee considers the evidence insufficient to justify a recommendation for or against routine therapeutic use of vitamin supplements in patients with extracranial carotid and vertebral artery disease 1.
- Lifestyle modifications, such as limiting alcohol consumption, quitting smoking, increasing physical activity, and adopting a Mediterranean diet rich in folate-containing foods, may be beneficial in reducing homocysteine levels.
- Regular monitoring of homocysteine levels is recommended every 3-6 months after initiating treatment, but the effectiveness of vitamin supplementation in reducing cardiovascular risk is unclear 1.
From the Research
Clinical Implications of High Homocysteine
- High homocysteine levels have been associated with an increased risk of cardiovascular diseases, including myocardial infarction, stroke, and peripheral vascular disease 2, 3, 4, 5.
- The relationship between homocysteine and cardiovascular disease is complex, with some studies suggesting that hyperhomocysteinemia is not directly responsible for cardiovascular disease, but rather a marker for underlying pathogenic mechanisms 2, 4.
- Reduced methylation potential, induced by elevated plasma homocysteine levels, may be the true responsible for cardiovascular diseases, leading to DNA hypomethylation and inhibition of endothelial cell growth 2.
- Folic acid and other B vitamins can lower plasma homocysteine levels, but the clinical benefit of this therapy is still uncertain 3, 4, 5.
- Some studies suggest that lowering homocysteine levels by B-group vitamins and/or folates does not reduce cardiovascular risk, despite normalizing homocysteine levels 2, 4.
- Elevated homocysteine levels have also been associated with other diseases, including Alzheimer's disease, neural tube defects, impaired childhood cognition, macular degeneration, and cognitive impairment in the elderly 3, 6.
- The clinical importance of homocysteine as a disease biomarker and guide for disease prevention is still being researched, with some studies suggesting that total homocysteine values in adults of 10 μmol/L or below are probably safe, while values of 11 μmol/L or above may justify intervention 6.