New national multicenter study: vitamins didn't cut stroke risk

February 03, 2004

CHAPEL HILL — Hopes that high doses of certain vitamins could help prevent a second stroke in people who already suffered one took a hit today as scientists released findings from a major multicenter study of that possibility.Their investigation showed no significant differences over two years between a group of 1,827 stroke patients receiving a high-dose mixture of folic acid, cobalamin (vitamin B12) and pyridoxine (vitamin B6) daily and a group of 1,853 others who took a low dose.The research, appearing in the Feb. 4 issue of the Journal of the American Medical Association, was coordinated by experts at Wake Forest University and the University of North Carolina at Chapel Hill. It involved patients at 56 institutions in the U.S., Canada and Scotland.

“High-dose vitamin therapy had no effect on prevention of strokes, coronary heart disease events or death in people with a prior stroke, which was disappointing,” said Dr. James F. Toole, professor of neurology at Wake Forest’s Baptist Medical Center and lead report author. “However, this does not mean they may not be effective in preventing them in younger patients.”

Besides Toole, report authors include Drs. Lloyd E. Chambless, professor of biostatistics, and Chin-Hua Wang, research investigator, both at the UNC School of Public Health. Chambless directs the biostatistics department’s Collaborative Studies Coordinating Center, which collected and analyzed patient data from all the participating medical centers and clinics.

“Previous work had shown an association between higher homocysteine levels in the blood and vascular problems such as stroke and heart attacks and that if you gave people folic acid and to some extent vitamin B6 and vitamin B12, you could lower their homocysteine levels,” Chambless said. “As a result, the idea arose that we might be able to reduce their risk of stroke and heart disease by giving them those vitamins. This research, which we called Vitamin Intervention for Stroke Prevention, or VISP, was to test that idea.”

Homocysteine is an amino acid produced during the breakdown of an essential amino acid known as methionine.

Researchers randomly divided the more than 3,600 patient volunteers, all of whom had suffered a stroke within the previous four months but were not disabled, in half and assigned them to the two groups, he said. The high-dose group received 2.5 milligrams of folic acid, 25 mg of vitamin B6 and 0.4 mg of vitamin B12 daily. People receiving the small doses got 20 micrograms of folic acid, 200 micrograms of vitamin B6 and six micrograms of vitamin B12.

The scientists found a persistent and graded association between homocysteine levels measured prior to starting the vitamins and how the patients eventually fared, Chambless said. Overall, lower levels were associated with somewhat fewer strokes, heart attacks and deaths than higher levels, even though there was no difference between high-dose and low-dose groups in those outcomes.

“Our monitoring board stopped the research, which was the first large trial testing the homocysteine hypothesis, when it became clear that the vitamins made no difference,” Chambless said. “One possible reason for the negative findings is that the federal government, around the time the study started, required that all breads, pastas and other foods made with processed grains be fortified with folic acid. As a result, the differences we produced in lowering homocysteine might not have been as large as we planned or large enough to show a difference.”

Another possibility is that elevated homocysteine is a marker — but not a cause — of vascular disease problems, he said. If so, reducing it would have little or no effect.

“Because our study and earlier studies have shown an association between total homocysteine levels in the blood and vascular problems such as stroke and heart attacks, longer-running studies in different patient populations are warranted,” Toole said.

The United States and Canada adopted the fortification regulation after scientists found that increasing folic acid in fertile women’s diets could reduce the number of babies born with devastating neural tube defects and certain other birth defects.

In an accompanying JAMA editorial, Dr. Daniel F. Hanley of Johns Hopkins Medical Institutions stressed that increasing exercise, stopping smoking and reducing blood pressure are important steps people can take to cut their risk of strokes. Clinicians as a group need to promote those and other stroke risk-reduction actions more aggressively, he said.

The National Institute of Neurological Disorders and Stroke supported the study. Roche Inc. of Paramus, N.J., provided raw materials for the vitamins.

This news release was researched and written by David Williamson of University News Services.

Note: Reach Chambless at (919) 962-3264, Toole through Jonnie Rohrer at (336) 716-6972 or Bob Conn at (336) 716-4587.

UNC News Services Contact: David Williamson, (919) 962-8596

UNC School of Public Health Contact: Lisa Katz, (919) 966-7467