White Grapefruit

Grapefruit is a hybrid fruit made from mixing pomelo and sweet orange.

There are three common varieties available: red, pink, and white. The names are based on the color of the fruit's pulp.

Effects on Estradiol 17beta-dehydrogenase Type 2

1-2 cups of white grapefruit juice potently inhibits Estradiol 17beta-dehydrogenase Type 2 (17bHSD2). Inhibition lasts approximately 4-8 hours.

Grapefruit juice contains the following inhibitors of 17bHSD2:

Blocking Psychedelic Action of Allylbenzenes

Anecdotal reports indicate that 2 cups of white grapefruit juice consumed 30 minutes before taking allylbenzenes will greatly reduce the psychedelic effects of allylbenzenes and delay their onset by up to 8 hours. The enzyme 17bHSD2 is required for allylbenzenes to produce psychedelic effects. Grapefruit juice potently inhibits this enzyme for 4-8 hours. See the article Oilahuasca Activation for more information.

Effects on the Cytochrome P450 Enzyme System

Among the varies types of grapefruit, white grapefruit has the strongest effect on P450 enzymes.

1 cup of grapefruit taken 3 times a day by human volunteers was found to inhibit CYP3A4 in small intestine (small bowel) epithelia (enterocytes) by 62%, but had no detectable effect on liver CYP3A4 activity, colon levels of CYP3A5, or small intestine concentrations of P-glycoprotein, CYP1A1, or CYP2D6.[8]

Grapefruit Oil

Grapefruit oil was found to inhibit CYP3A4 in vitro, but not CYP1A1 or CYP2D6.[9] Tests in humans are lacking for grapefruit oil but these results mirror those of grapefruit juice tested in humans.

Cytochrome P450 Enzyme Inhibitors in Grapefruit

P450 enzyme inhibitors found in grapefruit include:

Effects on Individual P450 Enzyme Levels From Juice

Enzyme Interaction Dosage Verified In Humans
CYP1A1 No Effect[8] 3 cups Yes
CYP1A2 23% Inhibition[3] 1-2 cups Yes
CYP1B1 ? ? ?
CYP2A6 Potent Inhibition [10] 1 Liter Yes
CYP2B6 Potent Inhibition 1-2 cups ?
CYP2C8 ? ? ?
CYP2C9 No Effect[7] 1-2 cups Yes
CYP2C19 No Effect[5] 300 ml Yes
CYP2D6 No Effect[8] 3 cups Yes
CYP2E1 No Effect[6] 1-2 cups Yes
CYP2F1 ? ? ?
CYP2J2 ? ? ?
CYP3A4 [1][2] 62% Inhibition[2][8] 3 cups Yes

1. J Clin Pharmacol. 2003 Aug;43(8):831-9;
Exposure-dependent inhibition of intestinal and hepatic CYP3A4 in vivo by grapefruit juice; Veronese ML, Gillen LP, Burke JP, Dorval EP, Hauck WW, Pequignot E, Waldman SA, Greenberg HE; Division of Clinical Pharmacology, Departments of Medicine and Biochemistry, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. PubMed PMID: 12953340
2. Interactions of Herbs with Cytochrome P450
Shufeng Zhou, Yihuai Gao, Wenqi Jiang, Min Huang, Anlong Xu, and James W. Paxton; DOI: 10.1081/DMR-120018248; 0360-2532 (Print); 1097-9883 (Online); Marcel Dekker, Inc. 2003; (Download Attached PDF Document)
3. Br J Clin Pharmacol. 1993 Apr;35(4):431-6;
Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man' Fuhr U, Klittich K, Staib AH; Department of Clinical Pharmacology, University Hospital Frankfurt/Main, Germany; PubMed PMID: 8485024
4. Br J Clin Pharmacol. 1999 Oct;48(4):543-52.
Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components; Eagling VA, Profit L, Back DJ; Department of Pharmacology and Therapeutics, University of Liverpool, Ashton Street, Liverpool, L69 3GE. PubMed PMID: 10583025
5. Formation of omeprazole sulphone but not 5-hydroxyomeprazole is inhibited by grapefruit juice
Wichittra Tassaneeyakul, Wongwiwat Tassaneeyakul, Suda Vannaprasaht, and Yasushi Yamazoe; 2000; PubChem PMCID: PMC2014902; PubMed PMID: 10671908
6. Chlorzoxazone, a selective probe for phenotyping CYP2E1 in humans.
Lucas D, Ferrara R, Gonzalez E, Bodenez P, Albores A, Manno M, Berthou F; PubMed PMID: 10471070
7. Effects of clarithromycin and grapefruit juice on the pharmacokinetics of glibenclamide.
Lilja JJ, Niemi M, Fredrikson H, Neuvonen PJ. PubMed PMID: 17223855
8. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.
Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W, Watkins PB. PubMed PMID: 9153299
9. Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents. Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins.
Schmiedlin-Ren P, Edwards DJ, Fitzsimmons ME, He K, Lown KS, Woster PM, Rahman A, Thummel KE, Fisher JM, Hollenberg PF, Watkins PB. PubMed PMID: 9351897
10. Effect of grapefruit juice on cytochrome P450 2A6 and nicotine renal clearance.
Hukkanen J, Jacob P 3rd, Benowitz NL. PubMed PMID: 17112808
11. Content of Potentially Anticarcinogenic Flavonoids of Tea Infusions,
Wines, and Fruit Juices Michael G. L. Hertog, Peter C. H. Hollman, and Betty van de Putte. 1993. DOI: 10.1021/jf00032a015
12. Variations in content of active ingredients causing drug interactions in grapefruit juice products sold in California.
Wanwimolruk S, Marquez PV. PubMed PMID: 16841515
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