What Is Homocysteine, and Why Measure It?
- Homocysteine is an amino acid. Amino acids are the building blocks of proteins. When proteins break down, elevated levels of amino acids like homocysteine may be found in the bloodstream.
- Homocysteine levels increase in the body when the metabolism to cysteine of methionine to cysteine is impaired. This may be due to dietary deficiencies in vitamin B6, vitamin B12, and folic acid.
- Having elevated levels of homocysteine in the blood (hyperhomocysteinemia) is associated with atherosclerosis and blood clots.
- You can't get homocysteine from your diet. It has to be made from methionine, another amino acid that is found in meat, fish, and dairy products. Vitamins B6 (pyridoxine), B12 and folic acid are needed to make this reaction occur.
- Foods containing methionine are transformed into homocysteine in the bloodstream. Homocysteine is converted in the body to cysteine, with vitamin B6 facilitating this reaction. Homocysteine can also be recycled back into methionine using vitamin B12-related enzymes.
- Cysteine is an important protein in the body that has many roles. It is involved in the way proteins within cells are folded, maintain their shape, and link to each other. Cysteine is a source of sulfide and is part of the metabolism of different metals in the body including iron, zinc and copper. Cysteine also acts as an anti-oxidant.
- If homocysteine cannot be converted into cysteine or returned to the methionine form, levels of homocysteine in the body increase. Elevated homocysteine levels have been associated with heart attack, stroke, blood clot formation, and perhaps the development of Alzheimer's disease.
What Is Homocystinuria, and How Is It Inherited?
Homocystinuria (meaning elevated homocysteine in the urine) is a rare, inherited disease in which affected persons have abnormally high levels of homocysteine due to abnormal metabolism of the amino acid methionine. This condition is associated with a number of different birth defects including abnormalities of the musculoskeletal system. In infants who have a family history of homocystinuria, early screening for elevated levels may help prevent future illnesses related to this metabolic defect. Moreover, infants and young children who have eye problems such as myopia (nearsightedness), changes in the lens of the eye, bone abnormalities, or unusual body shape may be screened for elevated homocysteine levels.
What Are the Health Risks for Elevated Homocysteine Levels?
Elevated homocysteine levels in the body do not cause any symptoms. However, elevated levels of it in the blood have been associated with health risks. Therefore, an elevated homocysteine level may be a risk factor for developing certain diseases and conditions. For example:
- Elevated homocysteine levels affect the interior lining of blood vessels in the body, increasing the risk of atherosclerosis or narrowing of blood vessels. This can result in early heart attack and stroke.
- There is a relationship between the levels of homocysteine in the body and the size of the carotid arteries that supply the brain with blood; the higher homocysteine level, the narrower (stenosed) the carotid artery becomes.
- The risk of deep vein thrombosis (DVT) and pulmonary embolism may be linked to elevated homocysteine levels.
- There may be a relationship between elevated homocysteine levels and broken bones, especially in the elderly.
- Alzheimer's disease and other types of dementia may be more frequently seen in patients with increased or elevated levels of the amino acid in the blood.
- In infants who have the genetic condition homocystinuria, the inherited abnormalities affect the body's metabolism of homocysteine to cysteine. This may result in dislocation of the lens in the eye, sunken chest, Marfan-type appearance (long thin body type), mental retardation, and seizures. Neonatal strokes may also be seen with high homocysteine levels.
- In pregnancy, homocysteine levels tend to decrease. Elevated homocysteine levels may be associated with some fetal abnormalities and with potential blood vessel problems in the placenta, causing abruption. There may also be an association with pre-eclampsia.
What Are Normal and Elevated Homocysteine Levels?
Most laboratories report normal homocysteine levels in the blood between 4 and 15 micromoles/liter (µmol/L). Any measurement above 15 is considered high. Optimal homocysteine levels are below 10 to 12.
Hyperhomocysteinemia has been classified into moderate, intermediate, and severe types based on the level of homocysteine and are:
- Moderate (15 to 30 µmol/L)
- Intermediate (30 to 100 µmol/L)
- Severe (greater than 100 µmol/L)
Does Alcohol Elevate Homocysteine?
While alcoholics tend to be malnourished and lacking in B vitamins, alcohol itself may independently cause homocysteine levels in the blood to rise.
Why Did My Doctor Order a
Elevated levels of homocysteine are associated with heart attack, stroke, and blood clots. If a person develops any of these diseases and does not have increased risk factors such as smoking, high blood pressure, high cholesterol, or diabetes, then the physician often looks for more unusual causes and risks, including checking homocysteine levels in the blood.
How to Lower Homocysteine Levels with Vitamin Supplement Treatment
The treatment for homocystinuria is vitamin supplementation with pyridoxine (vitamin B6), vitamin B12, and folic acid. The effects of vitamin treatment may be monitored by routine, scheduled blood tests. However, evidence to support the value of treating elevated blood levels of homocysteine (except in cases of severely high levels) in the general population is lacking. Therefore, it is not recommended that people be treated with vitamins to lower homocysteine levels as a way to prevent vascular disease.
Some patients do not respond to the vitamin supplementation and are considered pyridoxine-resistant. A diet low in methionine is recommended in addition to the B vitamins.
Vitamin B-12 Deficiency and Elevated Homocysteine Levels
Pernicious anemia, or vitamin B-12 deficiency, is a type of anemia that's caused by the body's inability to absorb vitamin B-12 from the gut. Symptoms take many years to appear, and when they do you may experience clumsiness, lack of coordination, and personality changes. One blood test used to diagnose this condition is a homocysteine blood test since elevated levels of homocysteine is characteristic of vitamin B-12 deficiency.
Who Should Have Their Homocysteine Levels Tested?
Infants blood and urine are often checked for elevated homocysteine levels if they have a family history of the disease, or if they have certain medical conditions including eye lens dislocations, unusual (Marfan type) body shape, mental retardation, or signs of stroke.
Younger adults who have an early heart attack, stroke, or blood clots are often screened for blood clotting abnormalities including homocysteine blood tests.
Homocysteine levels are also often measured when a patient suffers a heart attack or stroke and has no risk factors for that illness (smoking, high blood pressure, high cholesterol, diabetes).
At present it is not recommended that individuals consuming normal diets with adequate folate levels be screened for elevated homocysteine levels.
Can Lowering Homocysteine Levels Prevent the Risk of Heart Disease, Heart Attacks, and Strokes?
There is controversy whether lowering homocysteine levels affects the risk of vascular disease like heart attack and stroke. At present there is no proof to show that lowering these levels has any benefit in terms of disease prevention, so treatment aimed at lowering blood homocysteine levels is not recommended for most people who do not have severe hyperhomocysteinemia. Some studies suggest that lowering homocysteine levels may decrease the risk of stroke. However, while the overall risk of stroke decreased in these studies, the severity of the stroke and the amount of disability were not affected. More importantly, medications that affect platelet function such as aspirin, clopidogrel (Plavix), and aspirin-dipyridamole (Aggrenox) are recommended and are effective as secondary stroke prevention medications. There is uncertainty whether the risk of heart disease is affected.
Reviewed on 9/11/2017
Haque WM. Homocysteine and Pregnancy. Best Pract Res Clin Obstet Gynaecol. 2003 Jun;17(3):459-69
Saposnik G; Ray JG; Sheridan P; McQueen M; Lonn E. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009; 40(4):1365-72