Homocysteine
An amino acid intermediate in methionine metabolism — elevated levels damage blood vessel walls.
Optimal Range
< 10 μmol/L (optimal) · > 15 μmol/L (elevated)
Risk-Stratified Targets
| Population / Context | Target |
|---|---|
| Optimal | < 8 μmol/L |
| Normal | < 10 μmol/L |
| Mildly elevated | 10–15 μmol/L |
| Moderately elevatedInvestigate B12, folate, B6, and MTHFR status | 15–30 μmol/L |
| Severely elevatedUrgent evaluation required | > 30 μmol/L |
Why It Matters
High homocysteine is associated with increased risk of heart attack, stroke, and cognitive decline. It often reflects deficiencies in B6, B12, or folate, and can be corrected with targeted supplementation.
Understanding Homocysteine
Homocysteine is an amino acid produced during the metabolism of methionine. Under normal conditions, homocysteine is rapidly recycled — either converted back to methionine (requiring vitamin B12 and folate) or converted to cysteine (requiring vitamin B6). When these pathways are impaired, homocysteine accumulates and damages the endothelial lining of blood vessels.
Elevated homocysteine (hyperhomocysteinemia) is associated with increased risk of cardiovascular disease, stroke, venous thromboembolism, and cognitive decline including Alzheimer's disease. The mechanism involves direct endothelial toxicity, promotion of oxidative stress, and impairment of nitric oxide production — all of which accelerate atherosclerosis.
The most common causes of elevated homocysteine are deficiencies in B12, folate, and B6 — all of which are readily correctable with supplementation. MTHFR gene variants (present in ~40% of the population) reduce the enzyme that converts folate to its active form, often resulting in elevated homocysteine that responds to methylfolate supplementation. Other causes include kidney disease, hypothyroidism, and certain medications (methotrexate, phenytoin, metformin).
Key Research
Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis
Wald DS et al. · BMJ (2002)
Key finding: For each 5 μmol/L increase in homocysteine, risk of coronary heart disease increases by approximately 20%.
Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment
Smith AD et al. · PLoS One (2010)
Key finding: B-vitamin supplementation to lower homocysteine slowed the rate of brain atrophy by 30% in elderly patients with mild cognitive impairment.