Hyperhomocysteinemia: Most Effective Dietary Supplements

Hyperhomocysteinemia is defined as an elevated concentration of homocysteine in the blood. Homocysteine is a sulfur-containing amino acid resulting from the metabolism of methionine, an essential amino acid. Normally, homocysteine is metabolized via two main pathways: transsulfuration and remethylation. Normal homocysteine levels range from 5 to 15 µmol/L. Higher levels may indicate hyperhomocysteinemia, with levels classified as follows: • Mild: 15-30 µmol/L • Moderate: 30-100 µmol/L • Severe: >100 µmol/L0b.

Diagnosis

The diagnosis of hyperhomocysteinemia is based on specific blood tests measuring plasma homocysteine levels. The underlying causes of hyperhomocysteinemia should be explored, including deficiencies in vitamins B6, B9 (folic acid), and B12, as well as genetic mutations affecting the enzymes involved in homocysteine metabolism such as cystathionine β-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR).

Etiology

Hyperhomocysteinemia can be caused by congenital and acquired factors: Certain genetic abnormalities are responsible for abnormally high levels of homocysteine: • Homocystinuria: This rare disorder, caused by a severe CBS (cystathionine beta-synthase) deficiency, leads to very high levels of homocysteine in the blood, often exceeding 100 µmol/L. • MTHFR gene mutations: The C677T mutation, for example, can cause moderate hyperhomocysteinemia, with levels ranging from 30 to 60 µmol/L. Hyperhomocysteinemia can also be linked to external factors or medical conditions: • Vitamin deficiencies: Deficiencies in vitamins B6, B9 (folic acid), and B12 are common causes. • Renal insufficiency: The accumulation of homocysteine is common in patients suffering from this condition. • Lifestyle: Smoking, excessive coffee consumption, and a vitamin-poor diet increase homocysteine levels. • Underlying diseases: Hypothyroidism, inflammatory bowel diseases, or rheumatoid arthritis can play a role. • Medications: Some treatments, like antiepileptics, theophylline, levodopa, fibrates, or metformin, are also involved.

Complications

Hyperhomocysteinemia is associated with a higher risk of cardiovascular and thromboembolic complications, such as: • Arterial thromboses: including coronary diseases, strokes, and peripheral artery diseases. Mechanisms involved include increased platelet reactivity, thrombin generation, and oxidative stress, leading to endothelial dysfunction and early atherosclerosis​​. • Venous thromboses: such as deep vein thrombosis and pulmonary embolism, often observed in association with other risk factors like obesity​.

Treatment

The treatment of hyperhomocysteinemia primarily aims to reduce homocysteine levels in the blood and prevent thromboembolic complications: • Vitamin Supplementation: Vitamins B6, B9 (folic acid), and B12 are the main treatments to reduce homocysteine levels. These supplements can significantly decrease homocysteine levels, although their direct impact on preventing cardiovascular events remains a topic of debate. • Lifestyle Modification: Quitting smoking, reducing coffee intake, and adopting a balanced diet rich in B vitamins can also help manage homocysteine levels​.