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  • Also Known As:
  • Plasma Total Homocysteine
  • Urine Homocysteine
  • Homocysteine Cardiac Risk
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At a Glance

Why Get Tested?

To help determine if you are deficient in vitamins B6, B9 (folate) or B12; to determine if you are at increased risk of heart attack or stroke; to monitor those who have heart disease; sometimes to help diagnose a rare inherited disorder called homocystinuria in newborns

When To Get Tested?

When your health care provider suspects that you have a vitamin B6, B12 or folate deficiency; when you have had a heart attack or stroke and do not have traditional risk factors, such as unhealthy lipid levels

Sample Required?

A blood sample taken by needle from a vein

Test Preparation Needed?

You may be instructed to fast for 10 to 12 hours prior to this test; only water is permitted.

You may be able to find your test results on your laboratory’s website or patient portal. However, you are currently at Testing.com. You may have been directed here by your lab’s website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab’s website or portal, or contact your healthcare practitioner in order to obtain your test results.

Testing.com is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.

The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called “normal” values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are “within normal limits.”

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

Homocysteine is an amino acid that is typically present in very small amounts in all cells of the body. That is because the body normally converts homocysteine into other products quickly. Since vitamins B6, B12, and folate are necessary to metabolize homocysteine, increased levels of the amino acid may be a sign of deficiency in those vitamins. This test determines the level of homocysteine in the blood and/or urine.

Elevated homocysteine may also be related to a higher risk for coronary heart disease, stroke, peripheral vascular disease (fatty deposits in peripheral arteries), and hardening of the arteries (atherosclerosis). High levels of homocysteine increase the risk of blood clot formation in vessels and may lead to heart attack and stroke. Several mechanisms have been proposed for how homocysteine leads to cardiovascular disease (CVD) risk, but direct links haven not been confirmed. There are also several studies that indicate no benefit or lowering of CVD risk with folic acid and B vitamin supplements. So far, the American Heart Association does not consider it a major risk factor for heart disease.

A rare inherited condition called homocystinuria can also greatly increase homocysteine in the blood and urine. In the U.S., all babies are routinely tested for excess methionine, a sign of homocystinuria, as part of their newborn screening. If a baby’s screening test is positive, then urine and blood homocysteine tests are often performed.

Common Questions

How is it used?

The homocysteine test may be used the following ways:

  • A healthcare practitioner may order a homocysteine test to determine if a person has a vitamin B12 or folate deficiency. The homocysteine concentration may be elevated before B12 and folate tests are abnormal. Some healthcare practitioners may recommend homocysteine testing in malnourished individuals, the elderly, who often absorb less vitamin B12 from their diet, and individuals with poor nutrition, such as drug or alcohol addicts.
  • Homocysteine may be ordered as part of a screen for people at high risk for heart attack or stroke. It may be useful in someone who has a family history of coronary artery disease but no other known risk factors, such as smoking, high blood pressure, or obesity. However, the exact role that homocysteine plays in the progression of cardiovascular disease has not been established, so the utility of the screening test continues to be questioned. Routine screening, such as that done for total cholesterol, has not been recommended.

When is it ordered?

This test may be ordered when a health practitioner suspects that a person may have a vitamin B12 and/or folate deficiency. Signs and symptoms are initially subtle and nonspecific. People with an early deficiency may be diagnosed before they experience any overt symptoms. Other affected people may experience a variety of mild to severe symptoms that can include:

  • Diarrhea
  • Dizziness
  • Fatigue, weakness
  • Loss of appetite
  • Paleness
  • Rapid heart rate
  • Shortness of breath
  • Sore tongue and mouth
  • Tingling, numbness, and/or burning in the feet, hands, arms, and legs (with B12 deficiency)

Homocysteine testing may be ordered as part of assessing a person’s risk of cardiovascular disease, depending on the individual’s age and other risk factors. It may also be ordered following a heart attack or stroke to help guide treatment.

What does the test result mean?

In cases of suspected malnutrition or vitamin B12 or folate deficiency, homocysteine levels may be elevated. If an individual does not get enough B vitamins and/or folate through diet or supplements, then the body may not be able to convert homocysteine to forms that can be used by the body. In this case, the level of homocysteine in the blood can increase.

Studies from the mid- to late-1990s suggested that people who have elevated homocysteine levels have a much greater risk of heart attack or stroke than those with average levels. Investigating the link between high homocysteine levels and heart disease remains an active area of research. At present, however, the use of homocysteine levels for risk assessment of cardiovascular disease (CVD), peripheral vascular disease, and stroke is uncertain given that several trials investigating folic acid and B vitamin supplementation indicate no benefit or lowering of CVD risk.

Additionally, a 2012 study of multiple datasets, including 50,000 people with coronary heart disease, called the potential for a cause-and-effect relationship between homocysteine levels and heart disease into question. A 2015 review of studies concluded that although there is a relationship between the homocysteine and CVD, there is other evidence that precludes homocysteine in being considered a biomarker for the disease. The American Heart Association (AHA) does acknowledge the relationship between homocysteine levels and heart attack/stroke survival rates but doesn’t consider elevated homocysteine a major risk factor for CVD.

While the AHA does not recommend widespread use of folic acid and B vitamins to reduce risk of heart attack and stroke, it does promote a balanced, healthy diet and advises health care practitioners to consider overall risk factors and diet in managing cardiovascular disease.

Is there anything else I should know?

When test results suggest homocystinuria, liver or skin biopsy samples are sometimes tested to determine whether the enzyme cystathionine beta synthase (CBS) is present. The absence of this enzyme is the most common cause of homocystinuria. Genetic tests may be ordered to test for one or more of the most common gene mutations. If someone has a strong family history of early atherosclerosis or a family member has been diagnosed with homocystinuria, then that person should be tested for the gene mutation that was found in the family member.

Homocysteine levels can increase with age, when a person smokes, and with the use of drugs such as carbamazepine, methotrexate, and phenytoin. Homocysteine levels are lower in women than in men. Women’s concentrations increase after menopause, possibly due to decreased estrogen production.

My newborn had a homocysteine test done. Why?

A rare inherited condition called homocystinuria can greatly increase homocysteine in the blood and urine. Tests for both a urine and blood homocysteine may be used to help diagnose homocystinuria if a health care practitioner suspects that an infant or child may have this inherited disorder. In the U.S., all babies are routinely tested for excess methionine, a sign of homocystinuria caused by CBS dysfunction, as part of their newborn screening. If a baby’s screening test is positive, then urine and blood homocysteine tests are often performed. Greatly increased concentrations of homocysteine in the urine and blood mean that it is likely that an infant has homocystinuria and indicates the need for further testing to confirm the cause of the increase.

In homocystinuria, one of several different genes—most commonly the CBS (cystathionine beta synthase) gene—is altered, disrupting the function of CBS. CBS is an enzyme that acts in a biochemical pathway and is responsible for converting homocysteine to a molecule called cysteine. As a result of CBS dysfunction, methionine (an amino acid), homocysteine and other toxic byproduct substances build up in the body. Some of the excess homocysteine is excreted in urine (homocystinuria).

The buildup of homocysteine and other byproduct substances in the body leads to multi-systemic disorder. Babies with this condition will appear normal at birth but, if not treated, they will, within a few years, begin to develop signs such as a dislocated lens in the eye, a long slender build, long thin fingers, skeletal abnormalities, osteoporosis, and a greatly increased risk of thromboembolism and of atherosclerosis that can lead to premature cardiovascular disease.

The buildup can also cause intellectual disability, mental illness, slightly low IQ, behavioral disorders, and seizures. Some of those may be alleviated if the condition is detected early, which is why all states screen newborns for homocystinuria.

What are some good sources of folic acid and vitamins B6 and B12?

Cereal grains are the main source of folic acid, the synthetic version of folate, or vitamin B9. In addition, the Food and Drug Administration requires the addition of folic acid to grain products in this country. Good sources of vitamin B6 include fortified cereals, beans, poultry and fish, as well as some fruits and vegetables, including dark leafy greens, oranges, papayas and cantaloupe. Vitamin B12 can be found in red meats, poultry, fish, and other seafood, as it is only naturally found in animal products. However, it can also be consumed via fortified breakfast cereals or enriched nondairy milk such as soy or rice milk.

Could any medications I may be taking have an effect on my homocysteine level?

Yes. There are numerous drugs that may either increase or decrease the amount of homocysteine in your body. You should always keep your healthcare provider and pharmacist aware of any medications, traditional or herbal, that you are taking since they may affect the test results. Carbamazepine, methotrexate, nitrous oxide, and phenytoin can all cause increased levels of homocysteine. Azaribine also raises homocysteine levels, though it was prohibited by the FDA in 1976. Colestipol and niacin, both lipid-lowering agents, can also increase homocysteine levels. Oral contraceptives can also affect the metabolism of homocysteine.

View Sources

Sources Used in Current Review

Homocysteine Test. MedlinePlus. Available online at https://medlineplus.gov/labtests/homocysteinetest.html. Accessed on 8/28/18.

(July 7, 2015) Homocysteine and MTHFR Mutations. Circulation. Available online at https://www.ahajournals.org/doi/abs/10.1161/circulationaha.114.013311. Accessed on 8/28/18.

(2002) Emergent Cardiovascular Risk Factor: Homocysteine. Progress in Cardiovascular Nursing. Available online at https://www.medscape.com/viewarticle/431273_4. Accessed on 8/28/18.

Three of the B Vitamins: Folate, Vitamin B6, and Vitamin B12. Harvard T.H. Chan School of Public Health. Available online at https://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/vitamins/vitamin-b/. Accessed on 8/28/18.

(March 2016) Homocystinuria. Genetics Home Reference. U.S. National Library of Medicine. Available online at https://ghr.nlm.nih.gov/condition/homocystinuria#sourcesforpage. Accessed on 8/28/18.

(January 10, 2015) Role of homocysteine in the development of cardiovascular disease. Nutrition Journal. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326479/. Accessed on 8/28/18.

Sources Used in Previous Review

Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby’s Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO. Pp 488-490.

Stewart. D. (2004 July 26, Updated). Homocystinuria. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/001199.htm.

Picker, J. and Levy, H. (2005 August 15, Updated). Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency. GeneReviews [On-line information]. Available online at http://www.genetests.org/query?dz=homocystinuria.

(2005 September 23) Homocystinuria. Genetics Home Reference, Homocystinuria [On-line information]. Available online at http://ghr.nlm.nih.gov/condition=homocystinuria.

Genetic Fact Sheets for Parents, Amino Acid Disorders. Expanded Newborn Screening with Tandem Mass Spectrometry Financial, Ethical, Legal, and Social Issues [On-line information]. Available online at http://www.newbornscreening.info/Parents/aminoaciddisorders/CBS.html.

(2005 May 02, Reviewed). Genetic Fact Sheets for Professionals, Amino Acid Disorders. Expanded Newborn Screening with Tandem Mass Spectrometry Financial, Ethical, Legal, and Social Issues [On-line information]. Available online at http://www.newbornscreening.info/Pro/aminoaciddisorders/CBS.html.

Homocysteine May Trigger Strokes. JS Online. Available online at http://www.jsonline.com/alive/ap/feb01/ap-stroke-amino-ac021601.asp.

Homocysteine: An emerging age-related cardiovascular risk factor. Geriatrics. April 1999.

Donald W. Jacobsen, PhD, FAHA. Director, Laboratory for Homocysteine Research, Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH. (Fellow, American Heart Association; American Association for Clinical Chemistry member).

Pagana, K. D. & Pagana, T. J. (© 2007). Mosby’s Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 541-543.

Clarke, W. and Dufour, D. R., Editors (© 2006). Contemporary Practice in Clinical Chemistry: AACC Press, Washington, DC. Pp 434-435.

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What Is Homocysteine? American Heart Association [On-line information]. Available online at http://www.americanheart.org/presenter.jhtml?identifier=535. Accessed May 2009.

(Updated 2008 July). Familydoctor.org. [On-line information] Available online at http://familydoctor.org/online/famdocen/home/articles/249.html. Accessed May 2009.

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Baloghova, J. et. al. (2006 December 6). Homocystinuria. emedicine [On-line information]. Available online at http://emedicine.medscape.com/article/1115062-overview. Accessed May 2009.

(Updated 2008 December). Cardiovascular Disease (Non-traditional Risk Markers) – Risk Markers – CVD (Non-traditional). ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/CardiacDz/CVDRiskMarkerNontrad.html. Accessed May 2009.

National Academy of Clinical Biochemistry. Laboratory Medicine Practice Guidelines: Emerging Biomarkers for Primary Prevention of Cardiovascular Disease and Stroke (2009) Homocysteine and Cardiovascular Disease Risk. Pg. 51. PDF available for download at http://www.aacc.org/members/nacb/LMPG/OnlineGuide/PublishedGuidelines/risk/Documents/PublishedGuidelines.pdf.

Clarke R, Bennett DA, Parish S, Verhoef P, Dötsch-Klerk M, et al. (2012) Homocysteine and Coronary Heart Disease: Meta-analysis of MTHFR Case-Control Studies, Avoiding Publication Bias. PLoS Med 9(2): e1001177. doi:10.1371/journal.pmed.1001177. Accessed February 2014.

Pagana, K. D. & Pagana, T. J. (© 2013). Mosby’s Diagnostic and Laboratory Test Reference 11th Edition: Mosby, Inc., Saint Louis, MO. Pp 537-538.

(Updated Feburary 2012). Homocystinuria. MedlinePlus Medical Encyclopedia. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/001199.htm. Accessed February 2014.

(Updated 2010 July). Coronary Artery Disease | High Homocysteine Level: How It Affects Your Blood Vessels. Familydoctor.org. Available online at http://familydoctor.org/online/famdocen/home/articles/249.html. Accessed February 2014.

(Reviewed 2011 July). Homocystinuria. Genetics Home Reference. Available online at http://ghr.nlm.nih.gov/condition=homocystinuria. Accessed February 2014.

(Updated 20 January 2012). Homocysteine, Folic Acid and Cardiovascular Disease. American Heart Association. Available online through http://www.americanheart.org. Accessed February 2014.

Mandava P. et al. (Updated 2013 June 20). Homocystinuria/Homocysteinemia. Medscape Available online at http://emedicine.medscape.com/article/1952251-overview#a30. Accessed February 2014.

Baloghova, J. et. al. (Upated 2013 July 24). Dermetologic Manifestations of Homocystinuria. Medscape. Available online at http://emedicine.medscape.com/article/1115062-overview. Accessed February 2014.

(Updated January 6, 2013) National Newborn Screening and Genetics Resource Center. National Newborn Screening Status Report. Available online at http://genes-r-us.uthscsa.edu/sites/genes-r-us/files/nbsdisorders.pdf. Accessed February 2014.

(Updated May 26, 2013) The Screening, Technology And Research in Genetics (STAR-G) Project, Homocystinuria Factsheet. Available online at http://www.newbornscreening.info/Parents/aminoaciddisorders/CBS.html. Accessed February 2014.


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