From the Guidelines
Homocysteine is an amino acid derived from the metabolism of the essential amino acid methionine, and elevated levels are associated with increased risk of cardiovascular diseases and stroke. Homocysteine is not obtained from the diet but is created as an intermediate product in various biochemical processes 1. It is produced in the body during protein metabolism, specifically when methionine is broken down. Normal homocysteine levels typically range from 5-15 micromoles per liter.
Causes of Elevated Homocysteine Levels
The body requires adequate amounts of vitamin B6, vitamin B12, and folate to properly metabolize homocysteine; deficiencies in these vitamins can lead to elevated levels 1. Other causes of hyperhomocysteinemia include genetic defects in the enzymes involved in homocysteine metabolism, such as deficiencies of cystathionine-synthase and methylenetetrahydrofolate reductase (MTHFR), or a thermolabile variant of MTHFR 1. Decreased renal clearance of homocysteine in patients with chronic renal failure may also contribute to hyperhomocysteinemia 1.
Association with Cardiovascular Disease
Elevated levels of plasma homocysteine are associated with a 2- to 3-fold increased risk for atherosclerotic vascular disease, including stroke 1. However, recent investigations have found that the relationship between homocysteine levels and carotid IMT was eliminated after adjustment for other cardiovascular risk factors or renal function 1. A meta-analysis of epidemiological studies found a 19% reduction in stroke risk per 25% lower homocysteine concentration after adjustment for smoking, systolic BP, and cholesterol 1.
Management of High Homocysteine
Supplementation with B vitamins, particularly folate, B6, and B12, does not lower the risk of cardiovascular disease, according to recent large secondary prevention trials 1. The B-vitamins B6, B12, and folic acid have been studied for their potential to lower homocysteine levels, but the evidence suggests that homocysteine-lowering interventions do not reduce the risk of fatal/non-fatal myocardial infarction, stroke, or death by any cause 1. Lifestyle modifications, including a balanced diet rich in leafy greens, legumes, and other B-vitamin sources, may be recommended for individuals with high homocysteine levels. Homocysteine can be measured through a simple blood test, often recommended for individuals with a family history of heart disease or those with existing cardiovascular conditions.
From the Research
Definition of Homocysteine
- Homocysteine (Hcy) is a critical intermediate in methylation reactions, created from methionine and either converted back to methionine or transformed into cysteine 2.
- It is an amino acid containing a sulfhydryl group, and is an intermediate product during metabolism of the amino acids methionine and cysteine 3.
Biochemistry of Homocysteine
- The process of homocysteine conversion is aided through several enzymes and three vitamins, folic acid, B12, and B6 2.
- Balanced activity among the enzymes is essential for the cell's well-being, while its malfunction could raise homocysteine concentration which can lead to the onset of several pathological conditions 4.
Health Implications of Homocysteine
- Hyperhomocysteinemia is a known risk factor for coronary artery disease, and elevated levels of homocysteine have been found in a majority of patients with vascular disease 2.
- It is also associated with more than 100 diseases or conditions, including cardiovascular diseases, diseases of the central nervous system, developmental and age-related conditions 5.
- Elevated homocysteine levels can lead to the onset of cardiovascular disease, atherosclerosis, stroke, inflammatory syndromes, and neuronal pathologies including Alzheimer's and Parkinson's diseases 4, 3.
Reduction of Homocysteine Levels
- Daily supplementation with 0.5-5.0 mg of folic acid typically lowers plasma homocysteine levels by approximately 25% 2.
- Supplementation with vitamins B6, B12, and/or folic acid can reduce homocysteine levels in patients with mild cognitive impairment, with a mean decline of homocysteine concentration of 31.9% in the intervention arms 6.
- Calibrated assumption of correct doses of vitamins such as folic acid, vitamin B6, vitamin B12, and betaine may control hyperhomocysteinemia-related conditions 4.