Hyperhomocysteinemia: the 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 are between 5 and 15 µmol/L. Higher levels may indicate hyperhomocysteinemia, with levels classified as follows:nn• Mild: 15-30 µmol/Lnn• Moderate: 30-100 µmol/Lnn• Severe: >100 µmol/L​​.

Diagnosis

The diagnosis of hyperhomocysteinemia is based on specific blood tests measuring plasma homocysteine levels. nnThe underlying causes of hyperhomocysteinemia should be investigated, notably the deficiencies in vitamins B6, B9 (folic acid) and B12, as well as genetic mutations affecting 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:nnSome genetic abnormalities are responsible for abnormally high levels of homocysteine:nn• Homocystinuria: This rare disorder, caused by a severe deficiency of CBS (cystathionine beta-synthase), leads to very high concentrations of homocysteine in the blood, often exceeding 100 µmol/L.nn• MTHFR gene mutations: The C677T mutation, for example, can cause moderate hyperhomocysteinemia, with levels ranging from 30 to 60 µmol/L.nnHyperhomocysteinemia can also be related to external factors or medical conditions:nn• Vitamin deficiencies: Deficiencies in vitamins B6, B9 (folic acid) and B12 are common causes.nn• Renal insufficiency: Accumulation of homocysteine is common in patients with this condition.nn• Lifestyle: Smoking, excessive coffee consumption, and a vitamin-poor diet increase homocysteine levels.nn• Underlying diseases: Hypothyroidism, inflammatory bowel disease, or rheumatoid arthritis may play a role.nn• Medications: Some treatments, such as antiepileptic drugs, theophylline, levodopa, fibrates, or metformin, are also involved.

Complications

Hyperhomocysteinemia is associated with a higher risk of cardiovascular and thromboembolic complications, such as:nn• Arterial thromboses: including coronary artery disease, strokes (cerebrovascular accidents), and peripheral arterial disease. The mechanisms involved include increased platelet reactivity, thrombin generation, and oxidative stress, which lead to endothelial dysfunction and premature atherosclerosis​​.nn• Venous thromboses: such as deep vein thrombosis and pulmonary embolism, often observed in association with other risk factors like obesity​.

Treatment

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