Brian Henry or Trish Moreis
AHA News Media Relations
Omni Rosen Hotel
NR 98-4846 (StrokeConf/Vitamin)
ORLANDO, Feb. 7 -- A trio of B vitamins given to a group of people who had suffered a stroke reduced their homocysteine levels and improved biochemical "markers" in their blood that indicate injury to artery walls -- damage that can lead to strokes.
The biochemical markers are homocysteine, a natural byproduct of the body's metabolism of protein and other nutrients, and thrombomodulin, produced by the injured cells lining blood vessels. When these endothelial cells are injured, blood clots can form. Thrombomodulin is produced by the body to inhibit clots, which can block vessels to the brain and heart, resulting in heart attack or stroke.
The research was presented here today at the American Heart Association's 23rd International Joint Conference on Stroke and Cerebral Circulation.
"A short-term vitamin intervention can reverse the homocysteine-mediated adverse effects on blood-vessel cells," says Richard F. Macko, M.D., of the Baltimore Veterans Administration Medical Center and assistant professor of neurology and geriatrics at the University of Maryland. "It is remarkable that only three months of vitamin therapy can produce these kinds of changes."
High levels of homocysteine, which result from the metabolism of the amnio acid methionine, are known from laboratory studies to damage blood vessels.
Scientists reported significant reduction in these two biochemical markers in 27 patients who received a vitamin supplement with folic acid, B-6, and B-12 added to it, compared to 23 patients who got the vitamin preparation without the B vitamins.
The study was not designed to determine whether giving the B vitamins would reduce the risk of a second stroke, but the results show the ability to manipulate these markers and indicate the need for further work on the potential protective benefits of the B vitamins, says Macko. "It now appears, based on numerous epidemiological studies, that homocysteine increases the risk of stroke and heart attack even when elevated to mild amounts in the bloodstream," he adds.
The double-blinded placebo-controlled study followed up on the laboratory findings of several research groups that have investigated the adverse effects of elevated homocysteine on the endothelial cells lining the inner surface of blood vessels.
Macko and his colleagues randomly assigned 50 stroke survivors to one of two groups. One received the vitamin preparation with the B vitamins. In the second group, the B vitamins were not given. The study included 29 men and 21 women over the age of 50. Both groups received a multivitamin daily. Twenty-seven patients received five milligrams of folic acid, 100 mg of vitamin B-6 and one mg of vitamin B-12.
After three months of therapy, the researchers found those who took the supplemental B vitamins had lowered their blood levels of homocysteine and had significantly lowered their plasma thrombomodulin. The other participants had not.
Thrombomodulin is a key player in the protein C-thrombomodulin system, one of the body's natural defenses against inappropriate or excessive blood clotting. Increased thrombomodulin in the blood is considered a marker of endothelial-cell damage. The reduction in thrombomodulin seen in the people getting the B vitamins indicated a reduction in damage to the cells lining their blood vessels.
"When an endothelial cell is injured by homocysteine, not enough functioning thrombomodulin is made, but the cell does produce more of it," Macko says. "We're showing that by reducing homocysteine with the vitamin B therapy, we're reducing endothelial injury.
"The implication of this is that the effect of the vitamin therapy may not be just specific to individuals who have higher levels; there may be no threshold effect," Macko adds. Finally, neither group showed changes in their fibrinolytic system, another way in which the body protects against unhealthy clotting, in this case by cutting up a protein called fibrin that holds a blood clot together.
"One of the things to consider is that homocysteine probably interferes with a number of different cellular mechanisms and that lowering homocysteine may have multiple biological effects on endothelial cells," Macko says. "This is a complex topic that we are studying. The big gap in our information is: What happens in humans if you lower homocysteine?"
Co-authors include Steven Kittner, M.D., M.P.H., Dorothy Kimberly Cox, B.S., Anne Epstein, M.S., and Mary Sparks, R.N., University of Maryland School of Medicine; Helga Refsum, Ph.D., and Per Ueland, Ph.D., University of Bergen, Norway; and Constance Johnson, M.D., and Robert Wityk, M.D., Johns Hopkins University School of Medicine.
Media advisory: Dr. Macko can be reached at (410) 605-7060. (Please do not publish telephone numbers.)