Grapefruit pectin and juice health benefit, review of medication interactions, dosage of supplement
October 27 2016 by
Ray Sahelian, M.D.

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.