What is being tested?

This test determines the level of homocysteine in the blood. Homocysteine is a sulphur-containing amino acid that is normally present in very small amounts in all cells of the body. Homocysteine is a product of methionine metabolism, and methionine is one of the eleven ‘essential’ amino acids (amino acids that must be derived from the diet since the body cannot produce them). In healthy cells, homocysteine is quickly converted to other products.

Folic acid (folate) is one of the ‘B’ vitamins that is needed to metabolise homocysteine. Vitamin B12, another B vitamin, helps keep folate in its active form, allowing it to keep homocysteine levels low. Therefore, people who are deficient in these vitamins may have increased levels of homocysteine.

According to the National Heart Foundation and the American Heart Association (AHA), some evidence suggests that excess homocysteine may promote atherosclerosis by damaging blood vessel walls and supporting the formation of inappropriate blood clots, but there is not a direct link between the two. The benefit of using homocysteine levels for risk assessment of cardiovascular disease (CVD), peripheral vascular disease and stroke is uncertain given that several studies indicate no benefit or lowering of CVD risk with folic acid and B vitamin supplementation.

Homocysteine can be greatly increased in the blood and urine of people with a rare inherited condition called homocystinuria. This disorder is caused by an alteration in one of several different genes. The affected person has a dysfunctional enzyme that does not allow the normal breakdown of methionine. Because of this, homocysteine and methionine begin to build up in the person's body. A baby with this condition will appear normal at birth but within a few years will 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 build-up may also cause progressive mental retardation, behavioural disorders and seizures.

How is it used?

A doctor may order a homocysteine test to determine if a person has B12 or folate deficiency. The homocysteine concentration may be elevated before B12 and folate tests are abnormal. Some doctors may recommend homocysteine testing in malnourished patients, the elderly, who often absorb less vitamin B12 from their diets, and those with drug or alcohol addictions.

A doctor may order both a urine and blood homocysteine to help diagnose homocystinuria if there is suspicion that an infant may have this inherited disorder. In some states, babies are tested for excess methionine as part of their newborn screening. If a baby's test is positive, then urine and blood homocysteine tests are often performed to confirm the findings.

Homocysteine may also 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. Its utility for this purpose, however, continues to be questioned because the role, if any, that homocysteine plays in the progression of cardiovascular disease (CVD) has not been established. Routine screening, such as that done for total cholesterol, is not yet recommended.

When is it requested?

This test may be ordered when a doctor suspects that a person may have a B12 and/or folate deficiency or when a baby has signs or symptoms that suggest that he or she may have homocystinuria.

Homocysteine may be ordered as part of a cardiac risk assessment, depending on the patient's age and other risk factors. It may also be used following a heart attack or stroke to help guide treatment.

What does the result mean?

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

In newborn testing, 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.

Older studies (1995 to 1999) suggested that people who have elevated homocysteine levels have a much greater risk of heart attack or stroke than those with average levels. At present, however, the use of homscysteine 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. The American Heart Association does acknowledge strong evidence of a relationship between homocysteine levels and heart attack/stroke survival rates but stops short of calling elevated homocysteine a major risk factor for cardiovascular disease. Blockage of a coronary artery, a precursor to a heart attack, occurs with more than double the average frequency in people with homocysteine levels in the highest 25% as compared to those in the lowest 25%.

At present, a direct correlation between homocysteine levels and heart attacks has not been established but there does seem to be strong evidence of a relationship between homocysteine levels and heart attack/stroke survival rates.

Since measuring homocysteine levels to determine cardiac risk is a relatively new use for the test, the exact reference range has yet to be determined.

Is there anything else I should know?

There is a hereditary (genetic) form of homocystinuria – an increase of homocysteine in the urine – that causes a form of mental retardation, skeletal abnormalities, and premature cardiovascular disease. A gene mutation prevents an enzyme from breaking down homocysteine into products that can be excreted through the kidneys. The build-up of homocysteine thus becomes toxic to the body. The most common hereditary form results in both an increase in homocysteine and a decrease in folic acid. 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 the patient has a strong family history of early atherosclerosis or a family member has been diagnosed with homocystinuria, then the patient should be tested for the gene mutation that was found in the family member.

Homocysteine levels can increase with age, when a patient 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 oestrogen production.

Common questions

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

Green leafy vegetables and cereal grains are the main source of folic acid. Fruits and vegetables have significant amounts of vitamin B6, and vitamin B12 can be found in red meats, poultry, fish and other seafood. People with high homocysteine levels also may benefit from taking multivitamins to supplement this amount.

• Is there a difference in risk between men and women?

Homocysteine levels in women increase after menopause, possibly due to decreased oestrogen production. Even so, the risk for women does not appear to increase with moderately-elevated levels.

• Could any drugs 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 doctor and pharmacist aware of any drugs, traditional or herbal, you are taking, since they may interfere with the test results.

More information

RCPA Manual: Homocysteine