EBM Consult

Lab Test: Homocysteine Level

    Lab Test
    • Homocysteine
    • Measurement of homocysteine levels in plasma for the evaluation of conditions that alter the function or blood concentration of the B vitamins, especially folate and cobalamin.
    Reference Range
    • Adults:  0-12 micromol/L
    Indications & Uses
    • Cardiovascular (CV) disease related to suspected homocysteinemia, especially  when the plasma homocysteine level is greater than 13 to 15 micromol/L.  Note: however, there is no definite set point at which a homocysteine level correlates with an increased risk of CV events.  High levels cause damage to the arterial endothelium, leading to severe atherosclerotic lesions.
    • Pregnant women with early-onset pregnancy complications, women who have previous pregnancy complications or who have had a child with birth defects, and women with known vitamin deficiency or those at risk for vitamin deficiencies - elevated levels are associated with birth defects and pregnancy complications, secondary to placental vasculopathy.   
      • Women who have had complications with their pregnancy or have had a child with birth defects may consider to have a homocysteine measurement done 3 months postpartum. 
      • Women with known vitamin deficiency or those at risk for vitamin deficiencies should have regular homocysteine measurements, preferably before and once during pregnancy. 
    • Suspected cobalamin or folate deficiency - elevated levels are suggestive of folate or cobalamin deficiency.  Diagnosis should be confirmed by serum cobalamin and serum folate measurement.
    • Suspected homocystinuria - homocystinuria should be suspected in individuals with a total plasma homocysteine level > 100 micromol/L.  An increase in fasting total blood homocysteine of 40 times normal levels may be seen.  
      • Close to half of untreated persons homozygous for this mutation will experience arterial or venous disorders before the age of 30 years.
      • Diagnosis should be confirmed with urine homocysteine measurement.
    Clinical Application
    • Homocysteine is an intermediate amino acid formed during the metabolism of methionine and there is some evidence to suggest that elevated blood levels of homocysteine may act as an independent risk factor for ischemic heart disease, cerebrovascular disease, and peripheral arterial disease. 
      • It does this by possibly promoting the progression of atherosclerosis by causing endothelial damage, low-density lipoprotein (LDL) deposition, and vascular smooth muscle growth. 
      • Consideration for screening of the presence of hyperhomocysteinemia (levels > 15 mmol/L) should be considered in individuals with progressive and unexplained atherosclerosis despite normal lipoproteins and in the absence of other risk factors.  It is also recommended in patients with an unusual family history of artherosclerosis, especially at a young age. 
    • Dietary deficiency of vitamins B6, B12, or folate are essential cofactors involved in the metabolism of homocysteine to methionine and is the most common non-genetic cause of elevated homocysteine.  
    • Genetic defects encoding the synthesis of the enzymes responsible for the metabolism of homocysteine to cysteine or the remethylation of homocysteine to methionine are the most common familial cause of hyperhomocysteinemia. 
    • Increased levels may indicate:
      • Cardiovascular disease, cerebrovascular disease, peripheral vascular disease, cystinuria, vitamin B6 or B12 deficiency, folate deficiency, or malnutrition
      • Results are also increased in males, in postprandial, low physical activity, with smoking, with increased blood pressure or increased blood cholesterol level, renal impairment, or metabolic disease. 
    • Results may be decreased in pregnancy, due to hemodilution.
    Related Tests
    • Vitamin B12 and folate - blood levels of these substances are easily determined.  The results have an impact on levels of homocysteine.
    • Lipoproteins - also important predictors of cardiac atherosclerotic risks
    • Cholesterol and triglycerides - important predictors of cardiac atherosclerotic risks
    • Apolipoproteins - this test is used to measure apolipoprotein levels and may be a better indicator of atherogenic risks that total high-density lipoprotein (HDL) or total LDL
    Drug-Lab Interactions
    • Patients with a low intake of B vitamins have higher levels of homocysteine. 
    • Smoking is associated with increased levels. 
    • Drugs that may cause increased levels include: 
      • azaribine, carbamazepine, methotrexate, nitrous oxide, theophylline, and phenytoin.
    • Drugs that are associated with decreased levels include: 
      • folic acid, oral contraceptives, and tamoxifen.
    Test Tube Needed
    • EDTA, heparin, or sodium citrate tube (blue top or lavender top tubes)
    • Ideally, specimen should be drawn after a minimum 12-hour fast although specimen can be drawn fating or non-fasting, and before or after methionine loading. 
    • For methionine loading, the patient ingests approximately 100 mg/kg of methionine after fasting for 10 to 12 hours. 
    • Obtain blood sample.  Collect repeat blood samples at 2, 4, 8, 12, and 24 hours to compare levels of B vitamins and amino acids in the plasma.
    • Apply pressure or a pressure dressing to the venipuncture site and assess the site for bleeding.
    Storage and Handling
    • Centrifuge immediately or within 30 minutes to avoid false elevation caused by release of homocysteine from red blood cells.    If this is not possible, chill or place specimen directly on ice or in ice water immediately and until plasma is separated. 
    • Separate plasma from red blood cells within 1 hour of collection. 
    • Plasma sample may be stored for up to 4 days at room temperature, for several weeks if refrigerated, or for several years at -20°C.  After freezing, inhomogeneity of sample matrix may occur; thorough mixing of sample is required after thawing.
    What To Tell Patient Before & After
    • Explain the procedure to the patient.
    • Instruct the patient to fast for 10 to 12 hours before the test.  Meats contain elevated levels of homocysteine.
    • Horton GL. Homocysteine: clinical significance and laboratory measurement. Lab Med 2006;37(9):551-553.
    • Varga EA et al. Cardiology patient pages. Homocysteine and MTHFR mutations: relation to thrombosis and coronary artery disease. Circulation 2005;111:e289-293.
    • LaGow B et al., eds. PDR Lab Advisor. A Comprehensive Point-of-Care Guide for Over 600 Lab Tests.  First ed. Montvale, NJ: Thomson PDR; 2007.
    • Pagana K, Pagana TJ eds. Mosby's Manual of Diagnostic and Laboratory Tests. 5th Ed.  St. Louis, Missouri. 2014.
    • Welch GN et al. Homocysteine and atherothrombosis. N Engl J Med 1998;338:1042-1050.

MESH Terms & Keywords

  • Homocysteine