A well-designed clinical study has cast doubt on the hope that B vitamins would prevent heart attacks and strokes. Over 3000 subjects entered the WENBIT study, which tested the effects of B vitamin supplements on the risk of heart attack, unstable angina (chest pain from coronary heart disease), stroke, or death.
WENBIT Study Groups
Subjects were randomly assigned to one of four treatment groups:
- Daily folic acid (folate) and vitamins B12 and B6
- Folic acid and B12 Vitamin
- B6 alone
- Placebo
Results
Homocysteine levels fell 30% in the groups that received folic acid and B12. As expected, homocysteine levels did not fall in the vitamin B6 or placebo groups.
Because results from another study suggested B vitamin supplements may increase cancer risk, the study was terminated (median follow-up time was 38 months). There was no difference in cardiovascular events (heart attack, angina, stroke) or death among the four groups. “In this randomized, double-blind, placebo controlled trial, we could not detect any preventive effect of intervention with folic acid plus vitamin B12 or with vitamin B6 on mortality or major cardiovascular events among patients with mainly stable [coronary artery disease] undergoing intensive conventional treatment,” the researchers reported.
There was, however, an increase in cancers in the treated groups, an increase that just missed being statistically significant.
Comments
These results suggest that homocysteine may just be a marker of an underlying damaging process, and the damage continues no matter what the homocysteine level. Other studies have suggested the damaging process might be inflammation in the blood vessels.
Vitamin B6 (pyridoxine) was included in the WENBIT study because other studies have shown an association of low B6 levels and high heart attack rates. Vitamin B12 was included because it prevents a possible problem from giving folic acid alone.
This study showed similar results of another study, the NORVIT study, strengthening its conclusions.
An opposite finding had come from population studies. In 1998, the United States and Canada began mandatory fortification of foods with folic acid. One study found fewer strokes after the fortification began, suggesting a possible cause and effect. However, the downward trend in strokes had already started before the mandatory fortification laws, and many other dietary changes were also occurring.
The increased number of cancers in the treated group, although not enough to reach the usual statistical cut-off, was worrisome. It recalled that in another study, subjects taking folic acid to reduce the risk of colon cancer actually had an increased rate of colon cancers.
Strengths and Weaknesses
The strengths of this study are the number of subjects—over 3,000—and that it was randomized and double-blinded (during the trial, neither the subjects not the investigators knew who was assigned into each group).
Potential weaknesses: The study was conducted in Norway, where diet and other factors may be different than other countries. The study was interrupted before its anticipated termination date, and included only subjects who already had some heart or blood vessel disease. The study did not have enough subjects to detect a reduction of cardiovascular events of less that 20% from folic acid.
Important Note
Folate supplements for women in child-bearing ages are universally recommended to reduce the risk in babies of neural tube defects such as malformation of the spinal cord. The study reported here has no bearing on that important recommendation.
Reference
Journal of the American Medical Association. 2008;300(7):795-804
