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Grapefruit Enhances
Some Drugs Blocks Others Impacts Vinblastine
April 7, 1999. Grapefruit have been valued as part of an anti-prostate cancer
diet along with tomatoes and strawberries. Red-fleshed grapefruit contain
lycopene, an antioxidant that appears to help prevent prostate cancer. And
citrus fruit compounds, limonoids may have immune-boosting and anti-cancer
effects.
But substances in grapefruit have quite powerful effects on the body's
absorption of many widely-prescribed medications. New evidence suggests that
consuming grapefruit juice could interfere with a chemotherapy drug used for
prostate cancer, Vinblastine.
From Blood Pressure
Drugs to Chemo
Drinking a glass of grapefruit juice when taking certain medications has long
been known to help the body absorb the drug. This "grapefruit effect"
is distinct from the need for acidity to dissolve some tablets such a Nizoral
(ketoconazole). If you've been advised to drink orange juice along with Nizoral,
you should of course continue to follow your doctor's instructions.
A couple of years ago, studies showed that grapefruit improves absorption of
drugs including calcium channel blockers and HIV-protease inhibitors. Now comes
another twist. Grapefruits vary according to how and where they're grown. The
state of people's innards varies. More than one set of intestinal chemicals is
involved. And depending on the drug, the "grapefruit effect" could
either boost it or block it.
The latest study has found that grapefruit blocks absorption of some drugs. One
of the drugs blocked, Vinblastine, is used in chemotherapy for prostate cancer.
Scientists at the University of California at San Francisco (UCSF) reported last
week that laboratory tests on cells show that grapefruit juice may have a
negative impact on the body's absorption of many widely-prescribed medications
including Vinblastine.
Bombers in a Glass of Juice, Potent Metabolic Effects
The grapefruit effect was discovered by happy chance almost a decade ago when
scientists gave volunteers grapefruit juice to mask the taste of a medication. A
single glass can significantly increase the absorption of a number of commonly
used oral medications including nearly all calcium channel blockers (used to
control blood pressure), some sedatives, and some immunosuppressants and
protease inhibitors (used for transplants and to treat AIDS).
How the grapefruit effect works was unknown until Dr. Paul Watkins and
colleagues at the University of Michigan Medical Center in Ann Arbor reported in
May 15 1997 Journal of Clinical Investigation that grapefruit juice decreases
the amount of an enzyme, called CYP3A4, already known to be present in the small
intestine.
This narrowed the search for substances in grapefruit juice that affect drug
metabolism. Pinpointing these could enable manufacturers to produce safer and
more effective medications.
Dr. Watkins went on to isolate a pair of substances in grapefruit that do this.
In the November 1997 issue of Drug Metabolism and Disposition, he and his UM
colleagues reported that these two components act like suicide bombers,
attaching themselves to the CYP3A4 and stopping it from interfering with drug
absorption.
After taking grapefruit juice, everyone in the study had virtually the same
level of CYP3A4. Normally, indivuals vary in how much CYP3A4 their intestines
churn out. This normal variation, by affecting metabolism of drugs, impacts drug
safety. A dose that is right for one individual can be ineffective or even toxic
to another. The researchers were excited to realize that adding the active
substance in grapefruit to a medication could produce a drug for which a
standard dosage would be equally effective in everyone.
But not only are people's guts variable -- so are grapefruits.
The concentration of the active ingredients varies dramatically among
grapefruits and grapefruit juices, even within the same product line. This is
most likely, the researchers say, because of growing conditions in different
regions and because manufacturers typically buy their grapefruits from many
areas. "For this reason," Watkins said in November 1997, "it
would be preferable to add the active ingredient to pills, rather than just
taking medication with grapefruit products."
Asked what people who regularly take drugs that are metabolized by CYP3A4 should
do about grapefruit in their diet, Dr. Lown said, "Consistency is the
key." "If you regularly drink grapefruit juice, don't change. If you
are on these drugs and don't normally take them with grapefruit juice, you may
need to consult your physician before adding grapefruit juice to your
diet."
New Caution Over Blocking Interaction
In the latest study, published in the April 1999 issue of Pharmaceutical
Research, Dr. Andrea Soldner and other scientists at UCSF show that grapefruit
juice can actually inhibit the body's absorption of certain drugs including:
· Vinblastine
(for combating cancer)
· Cyclosporine
(for suppressing organ rejection following transplant)
· Losartan (for
controlling high blood pressure)
· Digoxin (for
treating congestive heart failure)
· Fexofenadine
(for alleviating allergy symptoms)
This blocking of
drug activity occurs because an unknown substance in grapefruit juice activates
a naturally-produced chemical, P-glycoprotein, in the intestinal tract. When
grapefruit juice interacts with P-glycoprotein, the result is an increased
likelihood that certain drugs will be stopped from entering the bloodstream.
"These findings help to clarify some major discrepancies we've noticed in
the impact of grapefruit juice on various types of medications," said Dr.
Leslie Benet, professor of Biopharmaceutical Sciences at UCSF and director of
the study. Patients already taking grapefruit juice with their medications can
continue to do so, he said. But patients on drugs identified as specifically
affected by this blocking effect, " may get a further increase in
absorption by taking their drugs a couple of hours after a glass of grapefruit
juice."
According to Dr. Benet, patients who have not previously taken their drugs with
grapefruit juice "should be very cautious in doing so, since we now
recognize, depending on the drug, that grapefruit juice may either increase or
decrease levels of drug in the blood, leading to potential concerns for toxicity
or lack of efficacy."
Citrus Limonoids May
Have Anti-Cancer Effects
Posted April 7, 1999. Limonoids, found in the skin of citrus fruits, could have
significant health benefits, scientists said last month at the American Chemical
Society conference. Limonoids may have anti-cancer effects.
Limonoids are compounds found in citrus fruits, usually in the peels. They
produce the bitter taste and zesty aroma. Citrus limonoids are present in
commercial orange juice at about the same level as vitamin C.
Some researchers think citrus limonoids may be responsible for health effects
previously attributed to vitamin C. A Japanese company, Wakayama Prefectual
Federation of Agricultural Co-operatives, is making an orange juice with triple
the level of limonoid glucosides.
Preliminary research found limonoids could prevent and halt cancer under
laboratory conditions. They had anti-cancer effects in animals and prevented the
spread of human breast cancer in a cell culture. Scientists are now exploring
their use more fully.
The effect in the human body and on other types of cancer has not yet been
tested. So far the work has progressed from cells to mice, the researchers
reported at the conference. Another team is testing the performance of 12
limonoids in preventing cancer in humans.
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