Homocysteine

Homocysteine: An amino acid produced by the body, usually as a byproduct of consuming meat. Homocysteine is made from another amino acid, methionine, and then in turn is converted into other amino acids.

Elevated levels of homocysteine in the blood appear to make for an elevated risk of cardiovascular (heart and vessel) disease. Levels of homocysteine as low as 12 micromoles per liter of blood plasma have been found associated with an increased risk of heart attack, stroke, peripheral vascular disease and venous thromboembolism (blood clots in the veins). A homocysteine level of 15 micromoles or above has a heart attack rate three times as high as normal. Even a level of 12 micromoles can double the coronary risk.

Homocysteine can damage blood vessels in several ways. It injures the cells that line arteries and stimulates the growth of smooth muscle cells. Homocysteine can also disrupt normal blood clotting mechanisms, increasing the risk of clots that can bring on a heart attack or stroke.

Elevated levels of homocysteine also appear to increase the chance of Alzheimer's disease. In a remarkable study published in The New England Journal of Medicine in 2002, a large contingent of elderly people free of dementia were studied prospectively (in a forward-looking way). The results were quite startling. An elevated blood plasma level of the amino acid homocysteine was found to be an independent predictor of the development of clinical dementia, usually due to Alzheimer's disease. The higher the homocysteine level, the more likely a person was to later develop Alzheimer's. When plasma homocysteine is at a high level (over 14 micromoles per liter of blood), the risk of Alzheimer's disease doubled. The strength of this association is very powerful.

The ways to bring down homocysteine are by eating less meat and by taking supplements of the B vitamins folic acid (folate), B6, and B12 that are needed by the enzymes that process homocysteine. (Homocysteine builds up when the amino acid methionine cannot be converted to cysteine because an enzyme is lacking or is present in inadequate amounts. The B vitamins folic acid (folate), B6, and B12 are crucial to these conversion enzymes.)

Since folic acid supplementation can reduce plasma homocysteine levels, a possible strategy to help prevent both heart disease and Alzheimer's may be to provide more folic acid.

Concern for homocysteine as a cardiovascular risk factor came first. It dates to 1969 when Dr. Kilmer S. McCully reported that children born with a genetic error of metabolism called homocystinuria that causes the homocysteine levels to be very high sometimes died at a very young age with advanced disease in their arteries. However, until the 1990's the importance of homocysteine in cardiovascular disease was overshadowed by cholesterol story.