More than a decade has passed since it was unintentionally discovered that grapefruit juice interacts with certain drugs. The coadministration of these drugs with grapefruit juice can markedly elevate drug bioavailability, and can alter pharmacokinetic and pharmacodynamic parameters of the drug. The predominant mechanism for this interaction is the inhibition of cytochrome P-450 3A4 in the small intestine, resulting in a significant reduction of drug presystemic metabolism. An additional mechanism is the inhibition of P-glycoprotein, a transporter that carries drug from the enterocyte back to the gut lumen, resulting in a further increase in the fraction of drug absorbed. Some calcium channel antagonists, benzodiazepines, HMG-CoA reductase inhibitors and cyclosporine are the most affected drugs. A single exposure to one glass of the grapefruit juice can usually produce the maximal magnitude of the interaction. See Diet for ideas on how to widen your dietary selection.
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Benefit
Am J Clin Nutr. 2015. Flavanones protect from arterial stiffness in
postmenopausal women consuming grapefruit juice for 6 mo: a randomized,
controlled, crossover trial. The objective of the present study was to address
the role of flavanones in the long-term effects induced by grapefruit juice (GFJ)
consumption on vascular function in healthy postmenopausal women. Forty-eight
healthy postmenopausal women aged 50-65 y within 3-10 y since menopause, a body
mass index (in kg/m(2)) of 19-30, and a waist size >88 cm completed this
double-blind, randomized, controlled, crossover trial. These volunteers were
randomly assigned to consume 340 mL GFJ/d, providing 210 mg naringenin
glycosides, or a matched control drink without flavanones for 6 mo each, with a
2-mo washout between beverages. The primary endpoint was the assessment of
endothelial function in the brachial artery by using flow-mediated dilation.
Blood pressure, arterial stiffness, and endothelial function in the peripheral
arterial bed were also evaluated as indicators of vascular function. These
measurements and blood collection for clinical biochemical markers were
performed in overnight-fasted subjects before and after the 6-mo treatment
periods. The mean ± SD carotid-femoral pulse wave velocity, which reflects
central aortic stiffness, was statistically significantly lower after
consumption of GFJ than after consumption of the matched control drink without
flavanones for the treatment effect. Endothelial function in macro- and
microcirculation, blood pressure, anthropometric measures, glucose metabolism,
and biomarkers of inflammation and oxidative stress were not affected by the
intervention. Regular grape fruit juice consumption by middle-aged, healthy postmenopausal
women is beneficial for arterial stiffness. This effect may be related to
flavanones present in grapefruit.
Grapefruit and drug Interactions
Furanocoumarins in the human diet irreversibly inhibit human cytochrome P450 3A4
(CYP 3A4) and are responsible for the grapefruit / drug interaction phenomenon.
Grapefruit juice can alter oral drug metabolism by different mechanisms.
Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by
100 to 300 ml of grapefruit juice or by whole grapefruit segments. As a result,
metabolism of the drugs is reduced and oral drug bioavailability increased.
Enhanced oral drug bioavailability can occur 24 hours after juice consumption.
This means there is more of the drug in the body, and hence side effects could
occur.
Grapefruit juice can augment oral drug
bioavailability. This was originally based on an unexpected observation from an
interaction study between the dihydropyridine calcium channel antagonist,
felodipine, and ethanol in which grapefruit juice was used to mask the taste of
the ethanol. Subsequent investigations showed that grapefruit juice acted by
reducing presystemic felodipine metabolism through down regulation of cytochrome P450 3A4 (CYP3A4) expression in the intestinal
wall. Since the duration of effect of grapefruit juice can last more than a day, repeated
grapefruit juice consumption can result in a cumulative increase in felodipine AUC and
C(max). Clinically relevant interactions seem likely for most dihydropyridines,
terfenadine, saquinavir, cyclosporin, midazolam, triazolam and verapamil and may
also occur with lovastatin, cisapride and astemizole. The
high variability of the magnitude of effect among individuals appeared dependent
upon inherent differences in enteric CYP3A4 protein expression such that
individuals with highest baseline CYP3A4 had the highest proportional increase.
At least 20 other drugs have been assessed for an interaction with grapefruit
juice metabolism mediated by CYP3A4 appear affected by grapefruit juice.
Clinically relevant interactions seem likely for most dihydropyridines,
terfenadine, saquinavir, cyclosporin, midazolam, triazolam and verapamil and may
also occur with lovastatin, cisapride and astemizole. The importance of these
interactions appears to be influenced by individual patient susceptibility, type
and amount of grapefruit juice and administration-related factors.
Grapefruit juice may augment colchicine oral bioavailability. Due to colchicine narrow therapeutic-index and severely toxic side-effects, awareness of this interaction is prudent.
The compound in grapefruit juice that affects how some drugs are absorbed in the body is due to an intestinal enzyme called CYP3A, which partially destroys drugs as they are absorbed. Grapefruit juice, like no other fruit juice, interferes with CYP3A, so the body ends up absorbing more of the drug. The substance in grapefruit juice that appears to be responsible is called furanocoumarin. This could make it possible to screen certain fruits or herbs to see if they contain furanocoumarins.
Grapefruit and statin drugs
Scientists at Hebrew University in Jerusalem divided 57 men and women who had
recently undergone coronary bypass surgery and whose blood cholesterol remained
high despite treatment with statin drugs into three groups. One group ate a
single serving of red grapefruit every day; another ate a serving of white
grapefruit and the third group had none. Otherwise, all three groups ate an
ordinary balanced diet. At the end of 30 days, the researchers found that the
grapefruit eaters—especially those eating red grapefruit—had significant
decreases in cholesterol, while the abstainers did not.
What it Means: Combining grapefruit and statins to treat stubbornly high
cholesterol levels is an experimental remedy that should be done only under
close medical supervision. Grapefruit contains antioxidant chemicals, which may
be responsible in part for the effect. But grapefruit also increases the body's
absorption of statins, which is why the drugs usually come with warnings not to
eat grapefruit or drink grapefruit juice. Too high a level of statins in the
blood can lead to serious muscle damage.
Testimonial by email
I am a victim of Lopid drug. I was drinking grape
fruit juice while I was taking Lopid. Also my doctor was giving me Lopid twice a day.
In your news letter please let tell peoples that do not eat or drink grape fruit
juice. Because so many peoples don't know & doctor won't tell them. My doctor is
still telling me that grape fruit or grape fruit juice have no interaction with
Lopid. When I was taking that time I start problem in my shoulders and arms. I
was unable to lift my arms up and put my cloths on. I talk to my doctor and he
said you may have arthritis. He sent me for a MRI. Then he sent me to another
doctor and he gave a cortisone shot in both shoulders. He was saying some thing
like other doctor. But I was lucky. One day I was reading WOMAN DAY magazine and
I read about interaction between Lopid and Grape fruit juice. I stopped taking
both and got well within a month.
Email
Does grapefruit or drinking grapefruit juice
increase the risk for breast cancer?
There have been conflicting reports on the relationship between
grapefruit juice or eating grapefruits and the risk for breast cancer. Based on
my reviews, I have no reason to be concerned. I think it is a great idea to
diversify one's food intake and not eat a large amount of one fruit all the time
or drink a large amount of one type of fruit juice all the time, but rather to
consume a wide variety.
Blood thinning
If grapefruit juice is considered a blood thinner, is grapefruit pectin also
considered a thinner? If it is, why can't I substitute the pectin for the baby
aspirin I take for a thinner.
Not enough studies have been done to determine the extent of blood
thinning potential of grapefruit pectin. There are different ways to thin the
blood and aspirin works in different ways than do certain herbs and dietary
supplements such as fish oils, ginkgo, etc
More on grapefruit juice and drug
metabolism
It may interfere with some medications prescribed to treat high blood pressure,
statin drugs to treat blood cholesterol, some anti-anxiety and antihistamine
medications, as well as some medications used to treat HIV/AIDS and
immunosuppressant drugs used after transplant operations.
Grapefruit juice is an inhibitor of the intestinal cytochrome P - 450 3A4 system, responsible for the first pass metabolism of many drugs. The P - glycoprotein pump, found in the brush border of the intestinal wall which transports many of these cytochrome P - 450 3A4 substrates, is also inhibited by grapefruit juice. By inhibiting these enzyme systems, grapefruit juice alters the metabolism of a variety of medications, leading to elevation of their serum concentrations. Most influenced are calcium channel antagonist and the statin group of drugs.
Hosp Pharm. 2013. Hidden sources of grapefruit in beverages: potential interactions with immunosuppressant medications. The interaction between grapefruit-containing beverages and immunosuppressants is not well defined in the literature. This study was conducted to investigate possible sources of grapefruit juice or grapefruit extract in common US-manufactured beverages. The goal was to identify those products that might serve as hidden sources of dietary grapefruit intake, increasing a transplant patient's risk for drug interactions.
I've read your info on grapefruit juice - drug
interactions with interest. Do you think eating grapefruit would decrease the
body's ability to metabolize toxins we encounter in everyday life, such as
pesticides, etc., so that they build up in the body more readily? I was drinking
grapefruit juice daily when my employer began spraying pesticides, and I became
very ill. I wonder whether the grapefruit juice made it difficult for me to
detoxify the chemicals.
This is a good question and I don't know the answer as to daily
drinking of grapefruit juice reduces the body's ability to detoxify certain
toxins. As a general rule, it is preferable to ingest a wide variety of fruits
and juices rather than one or two. There are dozens of different fruits and
fruit juices in many large grocery and health food stores and by ingesting a
variety of them we are exposed to beneficial substances from each while
minimizing potential problems from overexposure to just one or two.
Hormone influence
Nutr Cancer. 2013. The effect of grapefruit intake on endogenous serum
estrogen levels in postmenopausal women. Although grapefruit intake leads to
elevated serum estrogen levels when hormones are taken orally, there are no
published data on the effect on endogenous levels. We conducted a pilot dietary
intervention study among healthy postmenopausal volunteers to test whole
grapefruit, 2 juices, and 1 grapefruit soda. Fifty-nine participants were
recruited through the Love/Avon Army of Women. The study consisted of a 3-wk
run-in, 2 wk of grapefruit intake, and a 1-wk wash-out. Eight fasting blood
samples were collected. An additional 5 samples drawn at 1, 2, 4, 8, and 10 hr
after grapefruit intake were collected during an acute-phase study for 10 women.
Serum assays for estrone (E1), estradiol (E2), estrone-3-sulfate (E1S),
dehydroepiandrosterone sulfate, and sex hormone-binding globulin were conducted.
Whole grapefruit intake had significant effects on endogenous E1S. Peak effects
were seen at 8 hr, increasing by 26% from baseline. No changes in mean E1 or E2
with whole fruit intake were observed. In contrast, fresh juice, bottled juice,
and soda intake all had significant lowering effects on E2. The findings suggest
an important interaction between grapefruit intake and endogenous estrogen
levels. Because endogenous estrogen levels are associated with breast cancer
risk, further research is warranted.