- What is homocysteine (definition), and when was it discovered?
- What are hyperhomycysteinemia and homocystinuria, and how are the inherited (genetic)?
- How many people have elevated homocysteine levels, and who gets the condition?
- Does a lowering homocysteine level prevent heart attacks and strokes?
- How can homocysteine levels be lowered?
- Who should get tested for elevated homocysteine levels, and how is it treated?
What is homocysteine (definition), and when was it discovered?
In 1969, Dr. Kilmer S. McCully reported that children born with a genetic disorder called homocystinuria, which causes the homocysteine levels to be very high, sometimes died at a very young age with advanced atherosclerosis in their arteries. Homocysteine levels in the blood may be elevated for many reasons. More specifically, these reasons can be divided into severe genetic causes and other milder causes.
What are hyperhomycysteinemia and homocystinuria, and how are the inherited (genetic)?
In the genetic condition called homocystinuria, there is a deficiency or lack of an important mediator molecule (enzymes) in the complicated homocysteine breakdown pathway. This leads to severely elevated levels of homocysteine. In this rare and serious condition, there is a constellation of symptoms that include developmental delay, osteoporosis (thin bones), visual abnormalities, formation of blood clots, and advanced atherosclerosis (narrowing and hardening of blood vessels). This condition is mainly recognized in childhood.
Milder genetic variations are more common causes of elevated homocysteine levels (hyperhomocysteinemia). In these conditions, the mediator molecules malfunction and are less efficient because of minor abnormality in their structure. They also lead to elevation of homocysteine levels, although much milder than in homocystinuria, by slowing down the breakdown of homocysteine.
How many people have elevated homocysteine levels, and who gets the condition?
Mild elevation in homocysteine levels (hyperhomocysteinemia) are common, and seen in about 5% to 12% of the general population. In specific populations such as, alcoholics (due to poor vitamin intake) or patients with chronic kidney disease, this may be more common. The severe genetic form, homocystinuria, is rare (0.02%).
Does a lowering homocysteine level prevent heart attacks and strokes?
Currently, there is no direct proof that taking folic acid and B vitamins to lower homocysteine levels prevents heart attacks and strokes. However, in a large population study involving women, those who had the highest consumption of folic acid (usually in the form of multivitamins) had fewer heart attacks than those who consumed the least amount of folic acid. In this study, the association between dietary intake of folate and vitamin B6 and risk of heart disease was more noticeable than between dietary intake of vitamin B12 and heart disease, which was minimal.
Many other observational studies have been performed to assess the effect of folate and the other B vitamins on heart disease. Most of these studies have concluded that oral intake of folate has been associated to lower risk of heart disease, possibly because due to lowering of homocysteine levels. The relation between oral intake of vitamin B12 and B6 and heart disease was not as obvious in many of these studies. In one study, it was concluded that even in people with elevated homocysteine levels due to genetic reasons, oral intake of folate and possibly the other B vitamins was related to lower incidence of heart disease.
Most of these data, however, are obtained from observational studies rather than purely controlled scientific data. Therefore, it is important to mention that despite these studies suggesting an association between the intake of these vitamins and the lower incidence of heart disease, in general, there is no compelling clinical evidence to treat hyperhomocysteinemia other than homocystinuria (the severe genetic form) in regards to heart disease, stroke, or blood clots. As stated previously, homocysteine levels are not routinely measured in individuals with these problems.
How can homocysteine levels be lowered?
Eating cereals that are fortified with folic acid, and to a lesser extent vitamins B6 and B12, can lower blood homocysteine levels. These supplements may even be beneficial in people with mild genetic hyperhomocysteinemia to lower their homocysteine levels. However, it is noteworthy that so far there is no compelling data to support the treatment of hyperhomocysteinemia for prevention of heart disease or treatment of known heart disease or blood clots. Homocysteine levels are not routinely measured in people with heart disease (atherosclerosis) or other diseases.
Who should get tested for elevated homocysteine levels, and how is it treated?
Currently, there are no official recommendations as to who should undergo testing for homocysteine blood levels. Before more scientific data become available from the currently ongoing studies, many experts do not recommend a screening test for blood homocysteine levels, even in patients with unexplained blood clot formation. In addition, the consensus recommendation is against treating elevated homocysteine levels with vitamins to prevent heart disease. Rarely, a few specialists may test for elevated homocysteine levels in patients with early onset of blood clot formation, heart attacks, strokes, or other symptoms related to atherosclerosis, especially if these patients do not have typical risk factors, such as smoking cigarettes, diabetes, high blood pressure, or high LDL cholesterol levels and they suspect genetic causes
There is also no consensus as to the optimal dose of folic acid and other B vitamins for the treatment of elevated blood homocysteine levels. (For example, treatment of patients with high homocysteine levels may require higher doses of folic acid and other B vitamins than the amounts contained in a multivitamin.) Therefore, a decision regarding testing should be individualized after consulting with your doctor and/or a specialist in genetic diseases.
Healthy Heart Resources
American Heart Association. Homocysteine, Folic Acid and Cardiovascular Disease.
Abrahaham, MD, J.M. et al. The homocysteine hypothesis: Still relevant to the prevention and treatment of cardiovascular disease? Cleveland Clinic Journal of Medicine December 2010 vol. 77 12 911-918.
UpToDate. Overview of homocysteine.