Serum Homocysteine (Hcy)
Homocysteine is a sulfur-containing non-proteinogenic amino acid generated during the conversion of methionine to cysteine. Elevations reflect methylation cycle impairment and confer neurovascular toxicity.
Standard vs. Optimal Reference Rangesμmol/L
Standard reference intervals represent the statistical 95% distribution of unselected commercial populations. Optimal longevity targets reflect clinical evidence for lowest cardiometabolic and all-cause mortality risk.
Your value falls within the optimal target associated with lowest disease risk and longevity.
< 15.0 μmol/L
General reference distribution across unselected commercial populations.
6.0 - 9.0 μmol/L
Concentration target associated with minimal all-cause cardiometabolic mortality.
Molecular Mechanism & Clinical Purpose
Homocysteine requires remethylation to methionine via methionine synthase (requiring vitamin B12 and methylfolate) or transsulfuration to cystathionine (requiring vitamin B6). Hyperhomocysteinemia induces reactive oxygen species generation, endothelial dysfunction, and collagen synthesis degradation.
Differential Diagnosis
Elevated Levels (Hcy High)
- •MTHFR C677T polymorphism / genetic homocystinuria
- •Vitamin B12, B6, or Folate deficiency
- •Chronic kidney disease (impaired clearance)
- •Hypothyroidism
Low Levels (Hcy Low)
- •Rarely pathological; can indicate hypermethylation or high glutathione synthesis demand
Technical Reference & Deep Dive
Biochemistry & Enzymatic Pathways
Longevity Risk Architecture & Epidemiology
Pre-Analytical Caveats & Diagnostic Workup
Pre-Analytical Considerations:
Standard testing requires a 10 to 12 hour overnight fast to minimize postprandial chylomicron interference, although Hcy direct immunoassay is less sensitive to prandial state than calculated LDL-C. Avoid strenuous high-intensity exercise 24 hours prior to blood draw. Serum separator tubes (SST) or EDTA plasma should be centrifuged within 2 hours. High-dose biotin (>5 mg/day) supplementation may interfere with competitive streptavidin-biotin immunoassays, requiring a 48-hour washout period.
Reflexive Testing Protocol:
- Advanced Lipoprotein Particle Quantification (NMR spectroscopy or ion mobility LDL-P)
- Lipoprotein(a) [Lp(a)] baseline evaluation for genetic cardiovascular risk stratification
- Coronary Artery Calcium (CAC) score via non-contrast cardiac CT to evaluate calcified plaque burden
- High-sensitivity C-Reactive Protein (hs-CRP) to assess systemic vascular inflammatory tone
- Carotid intima-media thickness (CIMT) duplex ultrasound to assess subclinical atherosclerosis
Clinical Citations & Primary Literature (1)
- [1]Homocysteine and Dementia: An International Consensus Statement - Journal of Alzheimer's Disease (2021). PMID: 29480198
Associated Longevity Guides & Clinical Calculators
Medicine 3.0Explore comprehensive evidence-based clinical protocols, testing costs, and algorithmic calculators that incorporate Serum Homocysteine (Hcy) into overall healthspan optimization.