The study, led by Dr James F. Toole, director of the Stroke Research Center at Wake Forest University Baptist Medical Center, found nearly identical rates of recurrent strokes and heart attacks between participants on a high dose of folic acid, B6, and B12 vitamins and those taking a low dose.
"High-dose vitamin therapy had no effect on stroke prevention, coronary heart disease events or death in this study, which was disappointing," Toole said, reporting in today's issue of the Journal of the American Medical Association.
Previous studies have indicated an association between raised levels of total homocysteine and stroke and heart disease. Folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12) are known to reduce plasma homocysteine levels but lowering homocysteine has not yet been confirmed an effective strategy for reducing risk of stroke.
The double-blind study, called VISP (for Vitamin Intervention for Stroke Prevention), involved 3,680 adults who had already had a non-disabling stroke and were being treated at one of 56 centres in the United States, Canada and Scotland. Half of the patients were assigned to the high dose group (25 mg vitamin B6, 0.4 mg vitamin B12, and 2.5 mg folic acid) and half to the low dose, containing 200 micrograms of vitamin B6, 6 micrograms of vitamin B12, and 20 micrograms of folic acid.
Mean reduction of total homocysteine was greater in the high-dose vitamin group than in the low-dose group, but there was no treatment effect on any end point, reports the team.
The chance of an event (stroke, coronary heart disease or death) within two years was 18 per cent in the high-dose group and 18.6 per cent in the low-dose group. The risk of ischaemic stroke was 9.2 per cent for the high-dose and 8.8 per cent for the low-dose groups.
But vitamin therapy did lower levels of homocysteine and the role of the amino acid in predicting stroke risk did appear to be confirmed - in both the low dose and in the high dose vitamin group those with a high homocysteine level at the start of the study were the most likely to have a recurrent stroke.
"In summary, [this] trial showed that moderate reduction of total homocysteine level after ischaemic stroke had no effect on vascular outcomes during the two years of follow-up. However, because of the consistent findings of an association of total homocysteine level with vascular risk, further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary," the researchers conclude.
Just after the start of VISP, folate fortification of the US grain supply began (which increased folic acid in breads and other foods containing grains) and it became mandatory in January 1998. This 'profoundly reduced' the number of people with low levels of folate and high total homocysteine levels, Toole said.
The study was stopped in December 2002, (it was planned to end in May 2003), when its performance and safety monitoring board told the funding agency that "there was no chance of showing any difference between the two treatment groups during the remaining follow-up period".