Homocysteine

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.

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.

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.

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.

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.

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.

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.