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Nutrition, Vitamins & Supplements
Scientist Know Cause of Grapefruit Interaction with
Some Drugs
Furanocoumarins cause danger with blood pressure, cholesterol drugs
 May 9, 2006 – For years senior citizens have been
told by their doctors and pharmacists to avoid grapefruit juice, if they
are being treated with certain medications, including some drugs that
control blood pressure or lower cholesterol. Studies have shown that
grapefruit juice can cause more of these drugs to enter the blood
stream, resulting in undesirable and even dangerous side effects. Now,
researchers say they know why.
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New research from the University of North Carolina
at Chapel Hill has identified and established the substance in
grapefruit juice that causes the potentially dangerous interactions with
certain medications.
The drugs affected by grapefruit juice usually have
some difficulty entering the body after they are consumed because an
intestinal enzyme, CYP3A, partially destroys them as they are absorbed.
Grapefruit juice, but not other commonly consumed fruit juices, inhibits
this enzyme, allowing more of these drugs to enter the body.
It was originally assumed that the ingredients
responsible for drug interactions were the flavonoids that give
grapefruit juice its bitter taste.
The new study shows that a group of chemicals
called furanocoumarins are the likely culprit.
"This is the best evidence to date that
furanocoumarins are the active ingredients in grapefruit juice that
cause the interaction with medications," said Dr. Paul Watkins, the Dr.
Verne S. Caviness distinguished professor of medicine and director of
UNC's General Clinical Research Center (GCRC). Watkins led the study
team.
A report of the new findings appears in the May
issue of the American Journal of Clinical Nutrition.
Editor's Note: In a presentation in 2005,
researchers B.S. Buslig and J.A. Manthey of the USDA-ARS Citrus and
Subtropical Products Lab, reported on a study in which they also found
furanocoumarins (also known as psoralens) to be responsible for the
interactions between grapefruit and certain prescription drugs. The
report was to the Institute of Food Technologists 2005 Annual Meeting.
More on their study.
To determine whether furanocoumarins are
responsible for grapefruit juice-drug interactions, Watkins worked with
scientists at the Florida Department of Citrus to selectively remove
only the furanocoumarins from the juice.
He and his collaborators then studied the effect of
the whole juice versus furanocoumarin-free juice on the ability to
affect absorption of felodipine, an anti-hypertension drug known to
interact with grapefruit juice "And we found that removing the
furanocoumarins from grapefruit juice entirely got rid of this
interaction," Watkins said.
In this randomized study, 18 healthy volunteers
took 10 milligrams of felodipine with each of three juices: orange
juice, regular grapefruit juice, and grapefruit juice devoid of
furanocoumarins. Blood was collected over 24 hours to measure felodipine
blood levels. One week elapsed between each felodipine-juice
"treatment."
The study found that in contrast to whole
grapefruit juice, the furanocoumarin-free grapefruit juice behaved like
orange juice and did not cause an interaction with felodipine.
Watkins notes that there are several implications
of this work.
"First, it should now be possible to market the
furanocoumarin-free grapefruit juice to patients who would otherwise
need to avoid grapefruit. In addition, it should be possible to screen
new foods for the potential for drug interactions by determining whether
they contain furanocoumarins.
"Finally, it may be possible to add furanocoumarins
to formulations of certain drugs that tend to be poorly or erratically
absorbed to improve their oral delivery."
About the information source:
Co-authors with Watkins are Drs. Mary F. Paine,
research assistant professor in the UNC School of Pharmacy; Dr. Wilbur
W. Widmer, scientist with the Citrus and Subtropical Products
laboratory, U.S. Dept. of Agriculture; Dr. Heather L. Hart, GCRC
scientist; Susan N. Pusek, GCRC's director of faculty training; Dr.
Kimberly L. Beavers, former postdoctoral scientist in the GCRC; Anne B.
Criss, GCRC technician in Watkins' laboratory; and Drs. Sherri S. Brown
and Brian F. Thomas of the Research Triangle Institute.
Support for the study came from the National Center
for Research Resources and the National Institute of General Medical
Sciences.
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