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United States Department of Agriculture

Agricultural Research Service

Homocysteine - the new "bad guy"
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Eric O. Uthus

During the last decade, the amino acid homocysteine--which is produced naturally in the body--has drawn much attention as a potential contributor to heart disease when blood levels are elevated. More recently, scientists have suggested that elevated homocysteine may contribute to other age-related diseases, including vascular disease, osteoporosis, Alzheimer’s disease and other types of cognitive loss.

Homocysteine is formed when the body metabolizes another sulfur-containing amino acid, methionine. Normally, homocysteine is either degraded through a mechanism that uses vitamin B6, or it is metabolized back to methionine through one of two routes: one requires folic acid; the other requires vitamin B12.

Not surprisingly, researchers have found correlations between increased blood homocysteine and low intakes of vitamin B6, folic acid, or vitamin B12. On the other hand, people with lower concentrations of blood homocysteine have higher concentrations of vitamin B6, folic acid, and vitamin B12.

A normal concentration is around 10 micromoles per liter of plasma. Moderate concentrations range between 16 and 30 micromoles per liter; intermediate, between 31 and 100 micromoles per liter; and severe is more than 100 micromoles per liter.

Population studies have shown that people with cardiovascular disease have higher blood concentrations of homocysteine. But a correlation doesn’t prove that homocysteine itself is the true culprit. So a number of clinical studies are underway to see if lowering blood homocysteine concentrations will reduce cardiovascular disease. If the results are positive, public health professionals will likely develop strategies to insure that we consume enough vitamin B6, vitamin B12 and folic acid.

One question that researchers are attempting to answer is why is elevated homocysteine bad. Is it just a marker of some other metabolic product that is the direct cause, or is homocysteine itself the bad guy?

More and more evidence suggests that homocysteine is one of the bad guys. It can react with proteins and other biologically important compounds that contain sulfur groups, causing them to stop functioning. The extent of damage is related to how much homocysteine these compounds are exposed to and how long they are exposed. Given enough time, even moderately elevated concentrations of homocysteine will cause damage.

Homocysteine can also oxidize compounds; oxidation is suspected to be one cause of cardiovascular problems. Preliminary data suggests that vitamin C may help prevent this oxidative damage. It is also interesting to note that homocysteine thiolactone, which is easily formed in the body from homocysteine and is just as damaging as homocysteine, is detoxified by an enzyme in HDL cholesterol--the good cholesterol. Hence, this might be another explanation why HDL cholesterol has beneficial actions.

All of this goes to show, once again, that a well balanced diet with plenty of fruits and vegetables--excellent sources of vitamin B6, folic acid, and vitamin C--is a wise recommendation.

Last Modified: 10/23/2006
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