April 13, 2006|
Jennifer Tartaglia MS and Asher Kimchi M.D.
Ontario, Canada – Observational studies suggest that mild to
moderate elevations in homocysteine levels may increase
cardiovascular disease. Folic acid, vitamin B12, and vitamin B6
lower plasma homocysteine levels. The Heart Outcomes Prevention
Evaluation (HOPE) 2 study investigated whether supplementation
with folic acid and vitamins B12 and B6 reduce the risk of major
cardiovascular events in high risk patients. The trial found
that daily administration of folic acid and vitamins B6 and B12
lowered homocysteine levels but did not reduce the incidence of
major cardiovascular events. These results were published in the
April 13, 2006 issue of the New England Journal of Medicine.
The study was a randomized, double blind, placebo-controlled
trial. It enrolled 5522 patients over the age of 55 who had a
history of vascular disease or diabetes and other risk factors
for atherosclerosis. These participants were randomly assigned
to receive daily administration of a combination of 2.5mg folic
acid, 50mg vitamin B6, and 1mg vitamin B12 or matching placebo.
Patients were followed for an average of 5 years.
The investigators found that the change from baseline in
homocysteine levels between the 2 treatment groups was 0.4mg per
liter at two years and at the end of the study. The primary
study finding was that 519 patients (18.8%) in the
active-treatment group died of cardiovascular causes or had a
myocardial infarction (MI) or stroke (primary outcome events),
which was not significantly different from the 547 patients
(19.8%) in the placebo group (Relative Risk, 0.95; 95%
Confidence Interval, 0.84 to 1.07; P = 0.41). In addition, there
were no significant differences between treatment groups in any
The authors propose that the disparity between the
epidemiology of homocysteine and the results of clinical trials
may be partly due to homocysteine’s relationship to renal
dysfunction, smoking, increased blood pressure, and other
cardiovascular risk factors such as atherosclerosis. This
relationship helps to explain why homocysteine levels may be a
good marker, but not a direct cause, of vascular disease.
The findings presented in this study suggest that folic acid
and B vitamin supplements, while having an observable effect on
homocysteine levels, have no beneficial effect as a preventative
treatment for major vascular events in high-risk patients.
Authors (The Writing Group): Eva Lonn, M.D., Salim Yusuf,
D.Phil., M.B., B.S., Malcolm J. Arnold, M.D., Patrick Sheridan,
M.Sc., Janice Pogue, M.Sc., Mary Micks, C.T.R.C., Matthew J.
McQueen, M.D., Ph.D., Jeffrey Probstfield, M.D., George Fodor,
M.D., Ph.D., Claes Held, M.D., Ph.D., and Jacques Genest, Jr.,