Homocysteine is an amino acid that the body produces. Atypical homocysteine levels may indicate that a person has a deficiency in specific vitamins. It is also associated with a higher risk of cardiovascular disease.

Most people have low homocysteine levels. This is because the body breaks down the amino acid quickly into other compounds.

High, or elevated, homocysteine levels are known as hyperhomocysteinemia. This could indicate a person has a vitamin deficiency, as the body needs certain nutrients to break it down.

Less commonly, hyperhomocysteinemia can occur due to homocystinuria, which is a genetic disease. Homocystinuria means that the body is not able to process the building blocks of amino acids properly.

Read on to learn more about high homocysteine levels, including the symptoms, causes, and complications.

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Typical homocysteine levels are usually from 5–15 micromoles/liter (μmol/l). If the levels are above this, a person has hyperhomocysteinemia.

High homocysteine levels fall into three categories:

  • moderate, if from 16–30 μmol/l
  • intermediate, if from 31–100 μmol/l
  • severe, if over 100 μmol/l

According to a review of previous research in the journal Nutrition and Metabolism, the presence of high homocysteine can indicate a higher risk for developing a range of conditions but may not directly cause them.

A doctor may recommend a homocysteine level test if a person shows signs of a vitamin B6, B12, or folate deficiency or if they are at increased risk of heart disease, stroke, or heart attacks.

To perform the test, a doctor will draw a sample of blood. However, because the test involves quickly separating red blood cells from plasma, a doctor will need a centrifuge to do this. This is a piece of equipment that spins the sample around to separate the components.

If a doctor has a centrifuge, testing may take place in their office. Alternatively, they may require someone to visit a laboratory with the facilities to do this.

Before the test, a doctor may ask the person to fast for 8–12 hours, although they can drink water during this time. The doctor may also ask the person not to take medications or supplements before the test.

Hyperhomocysteinemia itself does not have any symptoms, but if it develops due to a deficiency in vitamins B6, B12, or folate, a person may experience:

  • weakness
  • dizziness
  • sores on the mouth or tongue
  • tingling in the feet, legs, hands, or arms
  • fatigue
  • pale skin
  • muscle weakness

One of the more common causes of high homocysteine is a B6, B12, or folate deficiency. This is because the body needs these nutrients to break down homocysteine. A lack of them can lead to a buildup of homocysteine in the blood.

Some people are more at risk of deficiencies in these vitamins than others. This includes people with:

  • restricted diets
  • vegetarian or vegan diets, as these can make it more difficult to get enough B12
  • MTHFR gene mutations, which impair the body’s ability to use folate

Some medications can also cause folate deficiency, including methotrexate, sulfasalazine, and pyrimethamine.

MTHFR gene mutations are also one of the potential causes of homocystinuria, which is a genetic condition that affects how the body processes the building blocks of amino acids, such as folate and B vitamins.

Other genes that can be involved include:

  • CBS
  • MTR
  • MTRR
  • MMADHC

Worldwide, around 1 in 200,000–335,000 people have homocystinuria. Many states test for the most common type of homocystinuria at birth.

However, high homocysteine is not always a sign of a medical condition or an indication of any serious problem. Sometimes, people have higher levels than is typical due to:

  • family history and genetics
  • smoking
  • alcohol consumption
  • age, as homocysteine levels appear to naturally increase over time
  • sex, as males are more likely to have higher levels than females

According to the Food for the Brain Foundation, the following medical conditions and medications may also contribute:

  • diabetes
  • rheumatoid arthritis
  • low thyroid hormone levels
  • certain medications, such as proton pump inhibitors, metformin, and methotrexate

High homocysteine levels are associated with a number of medical conditions, including:

However, this does not necessarily mean a person with high homocysteine levels will develop these conditions — only that prolonged high levels may raise the risk.

A 2017 meta-analysis states that healthcare professionals associate high homocysteine levels with a higher all-cause mortality risk. This means that there is a correlation between high homocysteine and an increased risk of death from any type of disease.

In the meta-analysis, for every 5 µmol/L increase in homocysteine levels, there was a 33.6% increase of all-cause mortality risk.

An older 2015 study also found a correlation between higher levels of homocysteine levels, folate deficiency, and cancer. But scientists are unable to predict what type of cancer a person may be at risk of based on this.

A doctor may recommend a blood test for homocysteine levels if the person has symptoms of vitamin B6, B12, or folate deficiency. They may also run the test if the person already has risk factors for heart disease.

If a person’s test results come back with high levels of homocysteine, a doctor may need to run additional tests to determine the underlying cause.

Treatment for high homocysteine levels will vary depending on the underlying cause. If it is due to a vitamin deficiency, dietary changes or supplements can help decrease the levels.

The following nutrients may help to lower homocysteine levels:

  • betaine
  • folic acid
  • vitamin B2
  • vitamin B6
  • vitamin B12
  • zinc

People with certain genetic differences or homocystinuria may need to take supplements and also follow a diet that limits protein throughout their lives.

However, whether lowering homocysteine reduces the risk of cardiovascular events or cancer is unclear. According to a 2017 review, no firm evidence so far suggests that this is the case, but a 2020 review states that folic acid supplementation to lower homocysteine will “likely” reduce the risk of vascular disease.

Furthermore, a 2019 review suggests that B vitamins, folic acid, and betaine may reduce the severity of conditions linked to hyperhomocysteinemia, including Alzheimer’s disease and cardiovascular disease.

Because researchers are still learning about the link between homocysteine and diseases, it is generally a good idea to take steps to keep levels within a typical range and to look after heart health by:

  • eating a balanced and heart-healthy diet
  • quitting smoking
  • reducing alcohol consumption

A doctor may want to follow up with another homocysteine test after several months to see if the levels are lowering.

Questions someone may wish to ask a doctor about their homocysteine levels include:

  • Are my homocysteine levels typical?
  • Should I be concerned about high levels?
  • What could be causing it?
  • Will you run tests to identify the cause?
  • What is the best way for me to reduce homocysteine?
  • When should I come back for another test?
  • What happens if the levels remain high?

Homocysteine is an amino acid. Typically, people have low levels of it in their blood as the body quickly breaks down homocysteine into other substances.

Elevated homocysteine could indicate a nutritional deficiency. Some people are more prone to these deficiencies and may need to take supplements or change their diet to ensure they get enough vitamins.

Consistently high homocysteine levels are associated with an increased risk of cardiovascular disease, cancer, and several other conditions. If a person is concerned about their homocysteine levels and what they mean, they should speak with a doctor.