Long known for its role in preventing anemia in
expectant mothers and spinal birth defects in
newborns, the B vitamin folate, found in leafy green
vegetables, beans and nuts, has now been shown
to blunt the damaging effects of heart attack when given in
short-term high doses to test animals.
In a new study, an international team of heart experts
at Johns Hopkins and elsewhere reports
that rats fed 10 milligrams daily of folate, also known as
folic acid or vitamin B9, for a week prior to
heart attack had smaller infarcts than rats who took no
supplements. On average, researchers say,
the amount of muscle tissue exposed to damage and scarred
by the arterial blockage was shrunk to
less than a tenth.
The team's findings, set for publication in the April
8 edition of the journal Circulation, come
just weeks after other international studies in humans
suggested that low-dose folic acid supplements
may prevent dementia in the elderly and in premature
births.
"We want to emphasize that it is premature for people
to begin taking high doses of folic acid,"
said senior study investigator David Kass, a professor at
the Johns
Hopkins School of Medicine and its
Heart Institute. "But if human studies prove equally
effective, then high-dose folate could be given to
high-risk groups to guard against possible heart attack or
to people while they are having one."
The more likely and most practical advantage to
ingesting supplements, he said, lies in folic
acid's potential to act as a short-term buffer for people
who may be having a heart attack and who
rush to the emergency room complaining of chest pain.
Clinical trials are expected in the near future,
although Kass said that a major challenge in testing is
that a high dose of folic acid for humans
comparable to that given the rats would require an
average-size adult to swallow more than 200 one-
milligram pills per day, "an impractical and unrealistic
regimen, even if the body excretes the excess."
In addition, "we do not yet know if folate is safe to
consume in this high a dose, or how much or
how little of it is needed to be effective," he said,
citing 25 milligrams per day as the highest dose
previously tested as safe to consume in adults. Kass said
that such a large amount of folate may also
yield unpredictable side effects. Some studies have linked
the nutrient supplement to increased rates
of colon and prostate cancer.
Each year, an estimated 565,000 first-time heart
attacks occur in the United States, with an
additional 300,000 recurrent heart attacks.
Results from the new study, conducted in rats —
dozens were fed supplements, and dozens more
did not receive any — showed that overall pumping
function during heart attack remained strong in
vitamin B9-fortified animals.
The amount of blood pumped by the treated hearts
during a 30-minute window when blood flow
to the heart was restricted to simulate a heart attack
stayed near normal for rodents, at an average
ejection fraction of 73 percent. Meanwhile, it fell in the
untreated group to 27 percent.
Similarly, the muscle wall at the front of the heart
kept contracting during heartbeats,
thickening by 37 percent in the supplement-fed group, but
the muscle could barely compress,
thickening by 5 percent, in the untreated group. (Sixty
percent would be the normal amount of
thickening in a healthy rat heart.)
Moreover, researchers found that an injection of folic
acid, within the first 10 minutes of a
heart attack, into the bloodstream of rats that had never
before taken supplements was almost
equally as effective as preventive therapy in reversing
muscle damage, and in lowering infarct size by a
factor of 10.
"Folic acid is already well-known to be safe to
consume in high doses in the short term, and it is
very inexpensive, costing pennies per milligram, so its
prospects look promising," said Kass, who is the
Abraham and Virginia Weiss Professor of Cardiol-ogy.
Researchers plan further tests to determine precisely
why folate protects the heart, and to
determine how effective it is in not-as-high doses. But
they point out that it has long been known for
its role in the normal workings of the cell's principal
energy source, the mitochondria, whose function
is essential to maintaining healthy blood vessels.
It was this evidence that led to the latest study,
which, said lead investigator An Moens,
suggests that folate acts as an energy reserve in the
heart, "providing much-needed energy for muscle
contraction, in the form of ATP, at the same time the heart
is being starved for oxygen-carrying
blood by a blocked artery."
According to Moens, then a postdoctoral cardiology
research fellow at Johns Hopkins, study
results showed that high-energy phosphate levels in the
blood of treated rats went down 43 percent,
but levels dropped by one-third more — by 66 percent
— in untreated rats.
"With more fuel, the heart kept pumping even though
its blood flow was reduced," said Moens,
now a cardiologist at the University of Antwerp in Belgium.
"The smaller heart attacks seemed related
to this better energy balance in the heart produced by the
folate."
In the study, heart function was monitored by more
than two dozen key tests, such as
echocardiogram and magnetic resonance imaging, as well as
by blood analysis before, during and after
the heart attack, when blood flow was allowed to resume in
the coronary artery that had been
blocked.
Among the team's other findings that backed up the
protective effects of folate on the heart
were mild, slight dips in systolic blood pressure during
heart attack in treated rats, while pressure fell
in untreated animals by 25 percent. Similarly, blood flow
was stable in the treated group but dropped
by 40 percent in untreated animals. PostÐheart attack
buildup of dangerous chemicals, known as
reactive oxygen species, was halved in treated rats. And
fatal arrhythmias, unstable heartbeats that
can immediately follow a heart attack, also went down, from
36.7 percent to 8.3 percent in the
supplement-fed group.
"In the future, we might just pop in an IV and give
people high-dose folate while they are
waiting for their catheterization or CT scans to search for
blockages," Moens said.
Funding for the study of folate, one of eight B
vitamins, was provided by the National
Institutes of Health and the Peter Belfer Laboratory
Foundation, with additional support from the
American Heart Association, Belgian American Educational
Foundations and University of Antwerp.
In addition to Kass and Moens, Johns Hopkins
researchers involved in this study were Hunter
Champion, Azeb Haile, Muz Zviman, Djahida Bedja, Kathy
Gabrielson and Nazareno Paolocci. Additional
researchers included Marc Claeys, Dirk Borgonjon, Luc Van
Nassauw, Floris Wuyts, Rebecca Elsaesser,
Paul Cos, Jean-Pierre Timmermans and Christiaan Vrints, all
of the University of Antwerp; and Barbara
Tavazzi and Guiseppe Lazzarino, of the University of Rome.
Further assistance with biochemical
analysis was provided by Pawel Kaminski and Michael Wollin,
of the New York University School of
Medicine.
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