From the Guidelines
Elevated homocysteine levels in the blood (hyperhomocysteinemia) should be addressed as they are associated with increased risk of cardiovascular disease, stroke, venous thrombosis, and possibly neurodegenerative conditions, although the evidence for direct treatment benefits is mixed. The implications of hyperhomocysteinemia are significant, with studies suggesting a 2- to 3-fold increased risk for atherosclerotic vascular disease, including stroke, as noted in the guidelines for the primary prevention of stroke 1. Key points to consider include:
- Hyperhomocysteinemia is caused by genetic defects, nutritional deficiencies (particularly of folic acid, vitamin B12, and vitamin B6), and decreased renal clearance of homocysteine.
- The relationship between homocysteine levels and cardiovascular risk is complex, with some studies suggesting a direct link and others indicating that the relationship may be confounded by other factors such as renal function 1.
- B-complex vitamins (folic acid, vitamin B12, and vitamin B6) can lower homocysteine levels, but evidence for their effectiveness in reducing cardiovascular events is limited, with several large randomized controlled trials (RCTs) failing to demonstrate a significant benefit 1.
- Dietary modifications, including increased consumption of foods rich in B vitamins, may also play a role in managing hyperhomocysteinemia.
- For individuals with genetic disorders affecting homocysteine metabolism, such as MTHFR mutations, higher doses or specific forms of supplements may be necessary.
- Regular monitoring of homocysteine levels is recommended to assess treatment effectiveness, although the clinical significance of lowering homocysteine levels remains unclear. Given the mixed evidence, a cautious approach is warranted, focusing on addressing underlying nutritional deficiencies and monitoring homocysteine levels, rather than relying solely on vitamin supplementation as a means to reduce cardiovascular risk.
From the Research
Implications of Hyperhomocysteinemia
The implications of hyperhomocysteinemia (elevated homocysteine levels) are significant and can have various effects on the body. Some of the key implications include:
- Arterial ischemic events, such as myocardial infarction (MI), stroke, or peripheral vascular disease 2
- Cardiovascular disease, with hyperhomocysteinemia being considered a novel risk factor or a powerful marker for cardiovascular diseases 2, 3
- Alterations in vascular morphology, loss of endothelial antithrombotic function, and induction of a procoagulant environment 3
- Oxidative stresses, which can lead to damage or injury to the body 3
Pathogenic Mechanisms
The pathogenic mechanisms responsible for cardiovascular disease appear to be dependent on DNA hypomeththesis, which induces an inhibition of cyclin A transcription and a reduction of endothelial cells growth 2. Additionally, reduced methylation potential (MP) induced by elevated plasma homocysteine levels seems to be the true responsible for cardiovascular diseases (CVD) 2.
Risk Factors
Hyperhomocysteinemia is associated with various risk factors, including:
- Folic acid deficiency, which is considered the most common cause of hyperhomocysteinemia 3
- Vitamin B12 and vitamin B6 deficiencies, which can also contribute to elevated homocysteine levels 3, 4
- Genetic factors, such as the C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene, which can predispose individuals to elevated plasma homocysteine 4
- Lifestyle factors, such as smoking, arterial hypertension, diabetes, and hyperlipidemia, which can additively or synergistically increase overall risk 3
Treatment and Prevention
Supplementation with B-vitamins, in particular with folic acid, is an efficient, safe, and inexpensive means to reduce an elevated tHcy level 5. However, whether this therapy confers a clinical benefit has yet to be determined, and testing for and treating elevated homocysteine is probably justified only in patients with known cardiovascular disease or who are at high risk 6.