Synonym

• Hcy
• Plasma total homocysteine

Tubes

• Lavender, green or red top tube
• 5 mL of venous blood

Additional information

• Fasting 10-12 hrs before the test
• Place on ice and send to the lab immediately or if delayed centrifuge the sample immediately and freeze within 1 hr of collection
• Handle sample gently to prevent hemolysis
• Tested in newborns at 3–5 days

Info

• The homocysteine test measures the concentration of homocysteine, an amino acid, in the blood stream
• Homocysteine, a sulfur containing amino acid, is produced from the synthesis of cysteine from methionine.
• Homocysteine is usually quickly metabolized to other compounds with the co-factors vitamins B₆, B₁₂, and folate
• Some studies suggest that an elevated homocysteine level increases risk of heart attack and stroke

Clinical

• The clinical utility of the homocysteine test includes:
• May be part of a cardiovascular risk assessment, depending on age and other risk factors. Patients most commonly screened will be those <40 yrs of age who have CVD, persons who have strong family history of heart disease but who do not have other risk factors that can be controlled such as smoking or high blood pressure
• Evaluate the risk of venous thrombosis or pulmonary embolism
• Individuals suspected with vitamin B₆, B₁₂ and folate deficiency, such as:
• Persons with unexplained macrocytic anemia
• Peripheral neuropathy or myelopathy
• Elderly people (>75 yrs of age) with malnutrition
• Vegetarians who are not taking vitamin B₁₂ supplement
• Persons with alcohol or drug addiction
• Persons using drugs that are folate antagonists, such as antiepileptics, methotrexate etc.
• Evaluation of recurrent spontaneous abortions or infertility
• Evaluation of delayed development or failure to thrive in infants suspected with inborn errors of metabolism
• As a part of neonatal screening in family history or high prevalence areas with homocystinuria
• Excess levels of homocysteine results in various pathological changes in the body such as:
• Damages the endothelial lining of blood vessels
• Changes in coagulation factor levels, increasing the risk of venous thrombosis
• Prevents smaller arteries from dilating, increasing the risk of plaque formation
• Causes platelet aggregation
• Causes smooth muscle cells lining the arterial wall to multiply, promoting atherosclerosis
• Persons with homocystinuria may clinically present with:
• Severe myopia
• Dislocated lens in the eye (lenticular subluxation)
• Ectopia lentis
• Malar rashes
• Livedo reticularis
• Tall, thin build, and long limbs
• High-arched feet (pes cavus)
• Knock-knees (genu valgum)
• Pectus excavatum
• Pectus carniatum
• Mental retardation
• Behavioral disorders and seizures
• Frequent thrombotic or thromboembolic phenomenon
• American Heart Association (AHA) recommends different grades of homocysteinemia as follows:
• <13 µmol/L: Desirable
• 15-30 µmol/L: Mild hyperhomocysteinemia
• 30-100 µmol/L: Moderate hyperhomocysteinemia
• >100 µmol/L: Severe hyperhomocysteinemia

(Reference values may change since bread has recently been fortified with folate)

• A 3µmol/L lower level of homocysteine lessens the likelihood of heart attack by 16%, stroke by 24% and deep vein thrombosis by 25%
• 5µmol/L lower level of homocysteine reduces the risk of death from all causes by 49%, death from cardiovascular disease by 50% and death from cancer by 26%
• It is unclear if modification of one’s homocysteine through folate supplementation results in any health benefit

Additional information

• There is day-to-day variation is about 10%
• Homocysteine blood levels are 30% higher in evening than in morning
• Higher levels are seen in men than women
• Levels increase with increasing age >40 yrs and after menopause in women
• This test is recommended every 3–5 yrs for persons with CVD
• Related laboratory tests include:
• Apolipoprotein A
• Apolipoprotein B
• Aspartate aminotransferase
• Atrial natriuretic peptide
• B-type natriuretic peptide
• Calcium (blood and)
• Cholesterol (total, HDL, and)
• Complete blood count
• C-reactive protein
• Creatine kinase and isoenzymes
• Folate
• Glucose
• Glycated hemoglobin
• Homocysteine urine
• Ketones
• Lactate dehydrogenase and isoenzymes
• Lipoprotein electrophoresis
• Magnesium
• Methionine Challenge Test
• Myoglobin
• Potassium
• Troponin I
• Troponin T
• Vitamin B₆
• Vitamin B₁₂

Nl Result

Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.

High Result

Conditions associated with elevated homocysteine levels (hyperhomocysteinemia) include:

• Genetic Defects (Homocystinuria
• Cystathionine synthase (CBS) deficiency
• Methylenetetrahydrofolate reductase (MTHFR) deficiency
• Methionine synthase deficiency
• Vitamin B₁₂ or coenzyme defect
• Nutritional Deficiencies
• Folate
• Vitamins B₆
• Vitamin B₁₂
• Medical Conditions
• Hypothyroidism
• Leukemias and carcinomas
• Pernicious Anemia
• Psoriasis
• Renal Failure
• Other
• Exercise
• Postprandial blood draw
• Pregnancy
• Smoking-Tobacco use
• Drugs
• Anticonvulsants
• Azauridine
• caffeine
• Carbamazepine
• Cycloserine
• Cyclosporine
• Ethanol
• Hydralazine
• Isoniazid
• Methotrexate
• Nitrous oxide
• Phenelzine
• Phenobarbital
• Phenytoin
• Theophylline

False positive increase in homocysteine levels when:

• The specimen is left standing at room temperature
• Hemolysis of the sample results in release of homocysteine from RBCs

Elevated homocysteine levels are a potential risk factor for various conditions such as:

• Women find it harder to conceive, have repeated early miscarriages and pregnancy complications such as pre-eclampsia, premature birth, very low birth weight and neural tube defects
• Poor neuro-cognitive function in adolescence
• Development of cardiovascular disease and vascular thrombosis
• Increased chances (82%)of developing stroke in individuals in highest homocysteine level quartile
• People with Type 2 Diabetes Mellitus are at greater risk of having high homocysteine than non-diabetics due to raised body insulin levels
• Homocysteine level of >10µmol/L increases the risk of dementia in individuals over 60 years old by 75% and levels >14µmol/L amplifies the risk of developing Alzheimer’s disease by 150%

Low Result

No pathologic conditions are associated with a low level of homocysteine.

• A 3µmol/L lower level of homocysteine lessens the likelihood of heart attack by 16%, stroke by 24% and deep vein thrombosis by 25%
• 5µmol/L lower level of homocysteine reduces the risk of death from all causes by 49%, death from cardiovascular disease by 50% and death from cancer by 26%
• It is unclear if modification of one’s homocysteine through folate, Vitamin B₁₂, and Vitamin B₆ supplementation results in any health benefit

Drugs, which decrease blood levels of homocysteine include:

• Estrogens
• Folic acid
• Penicillamine
• Pyridoxine
• Raloxifene
• Tamoxifen

References

• American Academy of Pediatrics®.Metabolic/Genetic Screening Activities. [Homepage on the Internet] ©2003. Last Updated on December 7, 2006. Last accessed on January 5, 2007. Available at URL: http://www.medicalhomeinfo.org/screening/newborn.html
• American Heart Association®. Homocysteine, Folic Acid and Cardiovascular Disease. [Homepage on the Internet] ©2006. Last accessed on January 5, 2007. Available at URL: http://www.americanheart.org/presenter.jhtml?identifier=4677
• Brown AS et al. Elevated Prenatal Homocysteine Levels as a Risk Factor for Schizophrenia. Arch Gen Psychiatry. 2007 Jan;64(1):31-39.
• eMedicine from WebMD®. Homocystinuria. [Homepage on the Internet] ©1996-2006. Last updated on December 6, 2006. Last accessed on January 5, 2007. Available at URL: http://www.emedicine.com/derm/topic708.htm
• Garibotto G et al. Causes of hyperhomocysteinemia in patients with chronic kidney diseases. Semin Nephrol. 2006 Jan;26(1):3-7.
• Genetics Home Reference®. Homocystinuria. [Homepage on the Internet] © 2001-2006. Last reviewed in August, 2005. Last accessed on January 5, 2007. Available at URL: http://ghr.nlm.nih.gov/condition=homocystinuria
• Irizarry MC et al. Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease. Neurology. 2005 Nov 8;65(9):1402-8.
• LabTestsOnline®. Homocysteine. [Homepage on the Internet] © 2001-2006. Last reviewed on November 14, 2005. Last accessed on January 5, 2007. Available at URL: http://www.labtestsonline.org/understanding/analytes/homocysteine/glance.html
• Lonn E, et al. Homocysteine Lowering with Foic Acid and B Vitamins in Vascular Disease. NEJM April 13, 2006. 354(15):1567-77.
• Nasir K et al. Elevated Homocysteine Is Associated With Reduced Regional Left Ventricular Function. The Multi-Ethnic Study of Atherosclerosis. Circulation 2007 Jan 2; [Epub ahead of print].
• UTMB Laboratory Survival Guide®. HOMOCYSTEINE. [Homepage on the Internet]© 2006. Last reviewed in February 2006. Last accessed on January 5, 2007. Available at URL: http://www.utmb.edu/lsg/LabSurvivalGuide/chem/Homocysteine.htm
• Yang F et al. Hyperhomocysteinemia and atherosclerosis. Sheng Li Xue Bao. 2005 Apr 25;57(2):103-14.