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Amino Acid's Heart Risks Tempered

Homocysteine not strong as a predictor among healthy people

TUESDAY, Oct. 22, 2002 (HealthDayNews) -- Elevations of a blood molecule implicated in heart attacks and strokes may be of less value in predicting those problems in healthy people than previously hoped.

Scientists have linked the substance, an amino acid called homocysteine, to heart and vessel disease. However, a new study found the connection was greatest when researchers tried to link homocysteine levels with illness in people already sick -- making the case for a causal connection tricky. When they looked over time in healthy people, however, the amino acid's impact on cardiovascular was modest at best and much lower than proven risk factors such as smoking and diabetes.

However, a second study released today found that people with a gene mutation that leads to elevated homocysteine levels are about 16 percent more likely than those with the normal version to develop coronary heart disease. The gene, MTHFR, produces an enzyme that helps the body process the nutrient folate. Since one of folate's jobs is to keep homocysteine in check, weakened MTHFR permits a rise in the heart-hostile molecule.

As a result, some experts say, it may still be worthwhile to recommend lowering homocysteine levels by taking folic acid supplements or by fortifying foods with the nutrient. The U.S. Food and Drug Administration has been ordering food makers to do so since 1998 because of folic acid's importance in fetal development.

Both studies appear in tomorrow's issue of the Journal of the American Medical Association.

In the first, a team led by Dr. Robert Clarke of Radcliffe Infirmary in Oxford, England, reviewed 30 previous studies that looked at homocysteine levels in more than 5,000 patients with ischemic heart disease, a condition in which the pump is starved of blood.

Clarke's group found the studies in which patients already had heart problems showed a stronger tie between homocysteine and the ailments than so-called "prospective" studies that followed healthy people over time.

After accounting for other heart risk factors such as smoking, high blood pressure and high cholesterol, the prospective studies taken together indicated that people with homocysteine levels 25 percent lower than average had an 11 percent smaller risk of heart disease and a 19 percent smaller risk of stroke. By comparison, diabetes doubles the risk of heart attacks and strokes and having high cholesterol raises the risk 50 percent.

The second study, led by Dutch researchers, also reviewed a pool of previous reports, these looking at the affect of a particular gene mutation on the risk of coronary heart disease. People with two copies of the error in what's called the MTHFR gene had about 25 percent higher homocysteine levels and about 16 percent greater risk of developing heart disease than those with the normal form of the gene.

The risk held among European men and women but not North Americans. The reason for the difference may be that Europeans tend to get less folate in their diet.

In a statement, Clarke says the two studies suggest a "modest but causal" link between elevated homocysteine and heart problems.

Folic acid supplements of between 0.5 and 5 milligrams a day can reduce blood levels of the amino acid by 25 percent, and several studies are now examining if boosting dietary folic acid can reduce the risk of heart attacks and strokes, Clarke says. "If such trials can show that lowering homocysteine levels can reduce vascular disease risk, then the implications for public health of decreasing the population mean level of homocysteine (by fortification of flour) could be substantial."

However, Dr. Peter W. F. Wilson, a Boston University folate expert, says that for most people, the risk of high homocysteine on heart health doesn't justify gene screening or a major public health initiative targeting the substance.

Only about 11 percent of the population in the United States has two bad copies of the MTHFR gene, which are required to cause folate problems, says Wilson, author of an editorial accompanying the journal article. Of those, perhaps 20 percent don't get ample folate, leaving roughly 2 percent of the nation in whom the combination of genetics and diet might substantially increase their risk of heart problems related to homocysteine, Wilson says.

However, for certain people, such as young men and women with cardiovascular problems, as well as those with kidney failure, doctors should consider looking for the amino acid, he adds.

What To Do

In addition to supplements, beans, orange juice, green leafy vegetables and several other foods are high in folic acid.

To find out more about homocysteine, try the American Heart Association or the American Council on Science and Health.

SOURCES: Robert Clarke, M.D., Clinical Trial Service Unit, Radcliffe Infirmary, Oxford, England; Peter W. F. Wilson, M.D., professor, medicine, Boston University Medical School; Oct. 23/30, 2002, Journal of the American Medical Association
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