What is a Homocysteine Lab Test?
A homocysteine lab test measures the total concentration of homocysteine (a sulfur-containing amino acid) in your blood plasma, primarily used to assess cardiovascular disease risk and identify vitamin B12, folate, or B6 deficiencies. 1
What Homocysteine Is
Homocysteine is a sulfur-containing amino acid produced as an intermediate metabolite when your body breaks down methionine, an essential amino acid obtained from dietary proteins like meat, poultry, eggs, seafood, and dairy products 2, 3
Approximately 70% of homocysteine in plasma is bound to albumin and other plasma proteins, with only trace amounts existing as free homocysteine 1
The body normally processes homocysteine through two pathways: remethylation (requiring folate and vitamin B12 as cofactors) and transsulfuration (requiring vitamin B6 as a cofactor) 4, 2
Normal Values and What Elevated Levels Mean
Normal range is 5-15 μmol/L in fasting subjects 1
Hyperhomocysteinemia is defined as levels >15 μmol/L after at least 8 hours of fasting 5
Even moderately elevated levels (10-15 μmol/L) may confer graded increased cardiovascular risks, though the definitive threshold remains 15 μmol/L 5
Clinical Significance
Elevated homocysteine is associated with a 2- to 3-fold increased risk of atherosclerotic vascular disease, stroke, and venous thromboembolism, making it an independent cardiovascular risk factor 6, 7
For every 5 μmol/L increase in homocysteine, stroke risk increases by 59% (95% CI, 29-96%) 6, 7
An increment of 5 μmol/L in total homocysteine confers equivalent coronary artery disease risk to a 20 mg/dL increase in plasma cholesterol 6
Elevated levels are also associated with increased total and cardiovascular mortality, dementia, Alzheimer's disease, bone fractures, and chronic heart failure 4
Critical Pre-Analytical Requirements
Blood samples must be placed on ice immediately after collection and centrifuged with plasma separation within 30 minutes to prevent falsely elevated results, as homocysteine increases by approximately 10% per hour at room temperature when plasma remains in contact with blood cells 1, 8
Fasting for at least 8 hours is mandatory for accurate results 5
Once properly separated and frozen, homocysteine is stable for months 1
Common Causes of Elevation
Vitamin deficiencies: folate, vitamin B12 (cobalamin), or vitamin B6 (pyridoxine) deficiency are the most common causes 1, 4
Genetic factors: MTHFR polymorphisms (especially C677T mutation) or cystathionine β-synthase deficiency 5, 7
Renal impairment: decreased clearance elevates homocysteine levels 7
Medications and other factors: certain drugs, hypothyroidism, poor diet, and advancing age can increase levels 5, 4
When Testing is Indicated
Testing should be ordered in specific clinical scenarios where results would change management, including 5:
- Unexplained venous thrombosis or premature atherosclerotic disease (before age 55 in men or 65 in women)
- Suspected vitamin B12, folate, or B6 deficiency requiring confirmation before treatment
- Strong family history of thrombotic events
- Comprehensive thrombophilia workup in patients with venous thromboembolism 5
Routine screening of asymptomatic individuals without personal or family history of thrombosis is not recommended 5
Critical Pitfall to Avoid
Never treat with folic acid alone without first ruling out vitamin B12 deficiency, as folate supplementation can mask the hematologic manifestations of B12 deficiency while allowing irreversible neurological damage to progress 5