Major furocoumarins in grapefruit juice I: Levels and urinary metabolite(s)

Messer, Anastasia; Nieborowski, Anna; Straßer, Christian; Löhr, Christiane V.; Schrenk, Dieter

doi:10.1016/j.fct.2011.09.005

Cited by 32 publications

(40 citation statements)

References 33 publications

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“…22 Bergamottin is found in grapefruit juice at a concentration of ~3-33 µmol/l and nootkatone at a concentration of ~2-3 µmol/l. 27,28 Considering the surprisingly strong interaction observed in the current study, it is plausible that grapefruit juice reduced clopidogrel bioactivation by inhibiting both CYP3A4 and CYP2C19. It should be noted that, in addition to the liver, CYP2C19 is also expressed in the small intestine 29 and could therefore participate in the activation of clopidogrel during the first pass in both the intestine and the liver.…”

Section: Discussionmentioning

confidence: 76%

“…Bergamottin and nootkatone inhibited the CYP2C19‐catalyzed 5‐hydroxylation of omeprazole with half‐maximal inhibitory concentrations (IC 50 ) of 0.3 µmol/l and 22.5 µmol/l (inhibition constant, K i : 0.5 µmol/l), respectively 22 . Bergamottin is found in grapefruit juice at a concentration of ~3–33 µmol/l and nootkatone at a concentration of ~2–3 µmol/l 27 , 28 . Considering the surprisingly strong interaction observed in the current study, it is plausible that grapefruit juice reduced clopidogrel bioactivation by inhibiting both CYP3A4 and CYP2C19.…”

Section: Discussionmentioning

confidence: 99%

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Grapefruit Juice Inhibits the Metabolic Activation of Clopidogrel

Holmberg

Tornio

Neuvonen

et al. 2013

Clin Pharmacol Ther

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Cytochrome P450 (CYP) enzymes, including CYP2C19 and CYP3A4, participate in the bioactivation of clopidogrel. Grapefruit juice constituents potently inactivate intestinal CYP3A4 and have been shown to inhibit CYP2C19 as well. In a randomized crossover study, 14 healthy volunteers ingested 200 ml of grapefruit juice or water three times daily for 3 days. On day 3, they ingested a single 600-mg dose of clopidogrel. Grapefruit juice reduced the peak plasma concentration (Cmax) of the active metabolite of clopidogrel to 13% of the control (range 11-17%, P < 0.001) and the area under the plasma concentration-time curve from 0 to 3 h to 14% (range 12-17%, P < 0.001) of the control, but it had no significant effect on the parent clopidogrel. Moreover, grapefruit juice markedly decreased the platelet-inhibitory effect of clopidogrel, as assessed with the VerifyNow P2Y12 test in two of the participants. In conclusion, concomitant use of grapefruit juice may impair the efficacy of clopidogrel. Therefore, the use of grapefruit juice is best avoided during clopidogrel therapy.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Grapefruit Juice Inhibits the Metabolic Activation of Clopidogrel

Holmberg

Tornio

Neuvonen

et al. 2013

Clin Pharmacol Ther

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“…Grapefruit (Citrus paradisi) juice is known for its ability to alter drug metabolism through inhibition of cytochrome P450-3A4 and results in drug-food interactions that may be life threatening . The primary active ingredients in Citrus responsible for these effects are the furanocoumarins bergapten, bergamottin, and 6 0 ,7 0 -dihydroxybergamottin (Guo et al, 2000;Paine et al, 2006;Fujita et al, 2008;Messer et al, 2011;Greenblatt et al, 2012). Studies have shown that Seville, mandarin, and clementine orange juices have the potential to produce drug interactions (see, for example, Abdelkawy et al, 2016;Theile et al, 2016), presumably due to their furanocoumarin content.…”

Section: Discussionmentioning

confidence: 99%

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

Stohs

2017

Phytotherapy Research

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Citrus aurantium L. (bitter orange) extracts that contain p‐synephrine as the primary protoalkaloid are widely used for weight loss/weight management, sports performance, appetite control, energy, and mental focus and cognition. Questions have been raised about the safety of p‐synephrine because it has some structural similarity to ephedrine. This review focuses on current human, animal, in vitro, and mechanistic studies that address the safety, efficacy, and mechanisms of action of bitter orange extracts and p‐synephrine. Numerous studies have been conducted with respect to p‐synephrine and bitter orange extract because ephedra and ephedrine were banned from use in dietary supplements in 2004. Approximately 30 human studies indicate that p‐synephrine and bitter orange extracts do not result in cardiovascular effects and do not act as stimulants at commonly used doses. Mechanistic studies suggest that p‐synephrine exerts its effects through multiple actions, which are discussed. Because p‐synephrine exhibits greater adrenergic receptor binding in rodents than humans, data from animals cannot be directly extrapolated to humans. This review, as well as several other assessments published in recent years, has concluded that bitter orange extract and p‐synephrine are safe for use in dietary supplements and foods at the commonly used doses. Copyright © 2017 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.

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“…Previous studies have found considerable differences on the content of various furanocoumarins in different varieties of grapefruit including different commercially available grapefruit juice brands (9, 31–33). However, the results of the present study suggest that factors other than the furanocoumarin content of various grapefruit products are at play.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Grapefruit Intake on Endogenous Serum Estrogen Levels in Postmenopausal Women

Monroe

Stanczyk

Besinque

et al. 2013

Nutrition and Cancer

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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.

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Major furocoumarins in grapefruit juice I: Levels and urinary metabolite(s)

Cited by 32 publications

References 33 publications

Grapefruit Juice Inhibits the Metabolic Activation of Clopidogrel

Grapefruit Juice Inhibits the Metabolic Activation of Clopidogrel

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

The Effect of Grapefruit Intake on Endogenous Serum Estrogen Levels in Postmenopausal Women

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