Two new studies question the conventional
wisdom that folic acid and B vitamin supplementation lowers
cardiovascular risk.
The logic behind supplementation has been that it reduces
blood levels of a protein called homocysteine, long linked
to heart attack and stroke. But the new research suggests
that lowering homocysteine this way has no effect on preventing
heart attacks -- and may even trigger a slight rise in
heart attack risk.
Both reports will appear in the March 16 issue of the
New England Journal of Medicine,
but were released early to coincide with their presentation
Sunday at the meeting of the American College of Cardiology,
in Atlanta.
"Combination vitamin therapies, which do lower homocysteine,
have no effect on cardiovascular events, even though the
homocysteine level is lowered," said Dr. Joseph Loscalzo,
head of the department of medicine at Brigham & Women's
Hospital in Boston, and author of an accompanying journal
editorial.
There was one glimmer of hope for people taking these
supplements, however: One of the two studies did note
a "marginally significant" decrease in stroke
risk after supplementation.
In the first study, called the Norwegian Vitamin (NORVIT)
trial, Norwegian researchers randomly assigned 3,749 men
and women who had heart attacks to receive folic acid,
vitamins B6 and B12, or a placebo.
Over the three years of the trial, the researchers found
that while homocysteine levels dropped an average of 27
percent among people taking folic acid and vitamin B12,
this decline in the blood protein had no significant effect
on whether people had another heart attack or died from
another heart attack.
In fact, people taking all three supplements actually
experienced a slightly increased risk of having another
heart attack, the researchers found.
"Doctors should not advise patients who have cardiovascular
disease to take B vitamins in order to prevent heart disease
or stroke," said lead author Dr. Kaare Harald Bønaa,
a professor of medicine and consultant cardiologist at
the Institute of Community Medicine at the University
of Tromsø. "B vitamins do not prevent heart
disease," he added.
In the second study, called the Heart Outcomes Prevention
Evaluation (HOPE) 2 study, researchers gave more than
5,500 patients who had diabetes or vascular disease folic
acid, vitamins B12 and B6, or a placebo.
Over the five years of the study, homocysteine levels
dropped significantly among those receiving the supplements,
but -- just as happened with the NORVIT trial -- this
lowering of homocysteine did not result in significantly
reduced risk of death from heart disease or heart attacks.
There did, however, appear to be a slight reduction in
stroke among people taking the supplements, the researchers
reported.
Overall, however, the researchers concluded that "combined
daily administration of 2.5 mg [milligrams] of folic acid,
50 mg of vitamin B6, and 1 mg of vitamin B12 for five
years had no beneficial effects on major vascular events
in a high-risk population with vascular disease."
They added that "our results do not support the
use of folic acid and B vitamin supplements as a preventive
treatment."
However, Anne Dickinson, a consultant and past president
of the Council for Responsible Nutrition, which represents
the supplements industry, said the findings may not apply
to relatively healthy Americans who are turning to these
vitamins to help ward off heart disease.
She noted that the two study populations involved sicker
individuals with a history of heart attack, heart disease,
diabetes and other problems.
"These studies did not test whether B vitamins used
by healthy people can help keep them healthy," Dickinson
said in a prepared statement. "Instead, they looked
at whether B vitamins can treat or reverse heart disease
in people who already have it. Vitamins should not be
expected to perform like drugs -- their greatest purpose
is in prevention."
But Alice H. Lichtenstein, director of the Cardiovascular
Nutrition Lab at the USDA Human Nutrition Research Center
at Tufts University, in Boston, countered that argument.
She noted that even outwardly "healthy" Americans
develop some level of atherosclerosis -- hardening of
the arteries -- as they age, and so the findings would
probably apply to the average consumer, as well.
Loscalzo thinks that the message from these studies
may not be that lowering homocysteine doesn't prevent
heart attacks, but rather that vitamin therapy is not
the best way to lower homocysteine.
"These trials of vitamin therapy for high homocysteine
have all been consistent in their message, namely, [that]
combination vitamin therapies, which do lower homocysteine,
have no effect on cardiovascular events, even though the
homocysteine level is lowered," he said.
Loscalzo said he believes the supplement treatment somehow
counteracts the effect of lowering homocysteine. "Some
of those adverse affects may have to do with the complex
metabolism of the vitamins," he said. "These
vitamins are important for cell growth. It may be that
the doses used might have stimulated the growth of cell
and atherosclerotic plaque."
According to Loscalzo, there's strong evidence that
homocysteine does adversely affect blood vessels. So perhaps
the answer lies in smaller doses of vitamins.
"These high doses of folic acid don't provide any
benefit and shouldn't be used," Loscalzo said. "Lower
doses are safe and may provide benefit, but we don't know
that yet.
"It's not that homocysteine is no longer a bad
actor," Loscalzo said. "It's that lowering it
with this simple treatment isn't the answer."
Lichtenstein agreed that high doses of vitamins may
not be as beneficial as some have thought.
"This is one of those cases where you see an association
with reduced risk of heart disease with levels of vitamins
that would normally be consumed, but when you go to considerably
higher levels than people could consume from diet, we
get disappointing results," she said.
