Slideshows Images Quizzes

Homocysteine (Normal and Elevated Levels Blood Test)

  • Medical Author: Charles Patrick Davis, MD, PhD
  • Medical Editor: William C. Shiel Jr., MD, FACP, FACR

What is the definition of homocysteine? What is it?

Homocysteine is an amino acid produced by the body by chemically altering adenosine. Amino acids are naturally made products, which are the building blocks of all the proteins in the body. Most labs report normal ranges of homocysteine as about 4-15 µml/L.

Can elevated homocysteine levels be genetic? When was homocystinuria discovered?

Homocystinuria was discovered in 1962 by two different groups of researchers. 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? Are they inherited (genetic)?

Homocystinuria was discovered in 1962 by two different groups of researchers. 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.

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%).

What are the signs and symptoms of homocystinuria?

Homocystinuria has a constellation of signs and symptoms that include:

  • Developmental delay
  • Osteoporosis (thin bones)
  • Visual abnormalities
  • Formation of blood clots
  • Advanced atherosclerosis or narrowing and hardening of blood vessels, a type of heart disease.

What are the more common causes of hyperhomocysteinemia?

More common causes of elevated homocysteine levels in the blood are milder genetic variations of homocystinuria. In these conditions, the mediator molecules malfunction and are less efficient because of a minor abnormality in their structure. They also lead to elevation of homocysteine levels (above 15 µmol/L), although much milder than in homocystinuria (above 100 µmol/L), by slowing down the breakdown of homocysteine.

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? How is it treated?

Currently, there are no official recommendations as to who should undergo testing for homocysteine blood levels. Before data that are more scientific 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. Some researchers recommend treatment guidelines that result in levels of homocysteine below 100 µmol/L but say the recommendation may change (possibly lowered) with new data.

Does 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. Homocysteine levels are not routinely measured in people with these problems.

Does lowering homocysteine levels 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. Homocysteine levels are not routinely measured in people with these problems.

Health Solutions From Our Sponsors

Reviewed on 6/28/2018

REFERENCES:

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.

Homocysteine, Folic Acid and Cardiovascular Disease.
<http://www.heart.org/HEARTORG/Encyclopedia/Heart-Encyclopedia_UCM_445084_ContentIndex.jsp>

Mandava, P, MD. Homocystinuria/Homocysteinemia. Medscape. Updated: Jun 14, 2017.
<https://emedicine.medscape.com/article/1952251-overview>

Morris, AM, et al, Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J. Inherit. Metab. Dis.. 2017; 40(1): 49–74. 40(1), 49-74. 2017 Published online 2016 Oct 24. doi: 10.1007/s10545-016-9979-0
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203861/>

Rosenson, RS, MD, et al. Overview of homocysteine. UpToDate. Updated: May 2018.
<https://www.uptodate.com/contents/overview-of-homocysteine>

Health Solutions From Our Sponsors