From the Guidelines
Elevated homocysteine levels, or hyperhomocysteinemia, increase the risk of stroke, cardiovascular disease, and potentially cognitive decline, but current evidence does not support the use of vitamin supplements as a treatment to reduce this risk. The effects of hyperhomocysteinemia include:
- Increased risk of stroke, with a 25% difference in plasma homocysteine concentration corresponding to a 19% difference in stroke risk 1
- Increased risk of developing extracranial carotid stenosis, with a 2-fold increase in risk among elderly patients with elevated homocysteine levels 1
- Potential contribution to cognitive decline, dementia, and Alzheimer's disease by damaging brain cells and blood vessels
- Potential impairment of bone health by interfering with collagen cross-linking, leading to osteoporosis and fractures The buildup of homocysteine occurs when the body cannot properly metabolize it, often due to genetic factors or deficiencies in B vitamins (particularly B6, B12, and folate) that are essential for homocysteine metabolism. While supplementation with B vitamins may lower homocysteine levels, studies have not confirmed a benefit of homocysteine lowering by B-complex vitamin therapy on cardiovascular outcomes, including stroke 1. Therefore, the use of vitamin supplements to treat hyperhomocysteinemia is not recommended, and other risk factors for cardiovascular disease should be addressed instead.
From the Research
Effects of Elevated Homocysteine Levels
Elevated homocysteine levels, also known as hyperhomocysteinemia, have been associated with various cardiovascular risks. The effects of hyperhomocysteinemia include:
- Increased risk of atherosclerosis, which is a serious and independent risk factor for cardiovascular disease 2, 3, 4, 5, 6
- Alterations in vascular morphology, loss of endothelial antithrombotic function, and induction of a procoagulant environment 3
- Increased risk of arterial and venous thromboembolism 4, 6
- Graded risk with no threshold, independent of but may enhance the effect of conventional risk factors 4, 5
- Particular strong predictor of cardiovascular mortality 4
Risk Factors and Interactions
Hyperhomocysteinemia can interact with conventional risk factors such as:
- Smoking, to substantially increase their effect on risk 5
- Arterial hypertension, diabetes, and hyperlipidemia, which may additively or synergistically increase overall risk 3
- Genetic and acquired factors, including deficiencies of folate and vitamin B12 3, 4
Prevention and Treatment
Prevention and treatment of hyperhomocysteinemia may include:
- Supplementation with B-vitamins, in particular with folic acid, to reduce an elevated homocysteine level 2, 3, 4, 5, 6
- Increased intake of fruits and vegetables 6
- Target plasma homocysteine level of < 10 micromol/l 3
- Reduction of elevated plasma homocysteine concentrations may theoretically prevent up to 25 percent of cardiovascular events 3