CYP3A4 is expressed in the liver, stomach, lungs, small intestine, and renal tissue.

CYP3A4 Inhibitors and Inducers

Potent Inhibitors Strength Dosage Verified In Humans
Black pepper extract 84.0% Inhibition[18] ? ?
Catechin (Green Tea) ? ? ?
Clove EO ? ? ?
Dillapiole [8] IC50=16.7 µM[7], <0.5 µM[14] 3-5 drops as dill oil CT dillapiole (unverified) ?
Eugenol (from in clove EO) ? ? ?
Ginger ? ? ?
Glabridin (in licorice)[11] 54%[17] IC50=10 μM ?
Licorice root extract (contains glabridin) [11] >70%[18] IC50=345 μM ?
Piperine (from Black pepper) ? 20 mg orally[21] Yes[21]
Pomegranate juice [12] ? ? ?
Quercetin ? 250-500 mg (unverified) ?
Silymarin (from Milk thistle) ? ? ?
Thymoquinone (in Nigella sativa)[19] ? ? ?
White Grapefruit 62%[5] 1-2 cups Yes[9]
Moderate Inhibitors Strength Dosage Verified In Humans
Berberine inhibition (40% increase in substrates)[25] 300 mg for 2 weeks[25] Yes[25]
Black Cumin seed (Nigella sativa) 41% inhibition1 2.5 g twice daily for seven days Yes[16]
Calamus oil [3] ? 3 drops (unverified) ?
Cinnamon ? ? ?
Curcumin ? 250 mg (unverified) ?
Goldenseal extract 40% Inhibition[10] 900 mg2, 3 times daily[10] Yes[10]
5-Hydroxyeugenol ? ? ?
Resveratrol[20] Only a 33% increase in substrates[23] 1 gram daily for 4 weeks[23] Yes[23]
Star fruit juice [13] ? ? ?
Turmeric ? ? ?
Weak Inhibitors Strength Dosage Verified In Humans
Alpha-asarone [3] ? ? ?
Capsaicin ? ? ?
Cayenne pepper ? ? ?
Common sage ? ? ?
Echinacea purpurea ? ? Yes[2]
Elemicin ? ? ?
German chamomile EO ? ? ?
Ginkgo biloba3 ? ? ?
Green Tea Extract ? ? ?
Habanero pepper ? ? ?
Methoxyeugenol ? ? ?
Methyl eugenol ? ? ?
Myristicin ? ? ?
Protocatechuic aldehyde ? ? ?
Saint John’s Wort (high dose) ? ? ?
In Vitro Inhibitors Inactive in Humans Strength Dosage Verified In Humans
Black cohosh Inactive ? Yes[10]
Garlic EO Inactive ? Yes[1]
Kava Inactive ? Yes[10]
Milk Thistle Inactive 200 mg 3 times a day Yes[15]
Panax ginseng Inactive 500 mg, three times daily, standardized to 5% ginsenosides Yes[24]
Potent Inducers Strength Dosage Verified in Humans
Saint John’s Wort [4] ? Low dose YES[6]
Valerian root ? ? ?
Inducers (unknown potency) Strength Dosage Verified In Humans
DHEA (dehydroepiandrosterone) ? ? ?
Ginkgo biloba ? ? Suggested by evidence [22]
Hyperforin ? ? ?
Nicotine ? ? ?
Rifampin ? ? ?
Tangeretin ? ? ?
Clin Pharmacol Ther. 2002 Sep;72(3):276-87. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY.; Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, 72205, USA; PubMed PMID: 12235448
2. Clin Pharmacol Ther. 2004 Nov;76(5):428-40;
In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto; Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Carrier J, Khan IA, Edwards DJ, Shah A.; Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, College of Pharmacy, Little Rock, 72205, USA. PubMed PMID 15536458
3. Fitoterapia. 2011 Apr;82(3):369-74. doi: 10.1016/j.fitote.2010.11.009. Epub 2010 Nov 6;
Metabolism mediated interaction of α-asarone and Acorus calamus with CYP3A4 and CYP2D6; Pandit S, Mukherjee PK, Ponnusankar S, Venkatesh M, Srikanth N; School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India; PubMed PMID 21062640
4. Shu-Feng Zhou, Zhi-Wei Zhou, Chun-Guang Li, Xiao Chen, Xiyong Yu, Charlie
Changli Xue, and Adrian Herington Identification of drugs that interact with herbs in drug development; Drug Discovery Today 12(15-16):pp. 664-673; Adrian (2007) (Download Attached PDF Document)
5. 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)
6. Komoroski BJ, Zhang S, Cai H, Hutzler JM, Frye R, Tracy TS, Strom SC, Lehmann T, Ang CY, Cui YY, Venkataramanan R;
Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures; Drug Metab Dispos. 2004 May;32(5):512-8; Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA; PubMed PMID: 15100173
7. Tepy Usia, Hiroshi Iwata, Akira Hiratsuka, Tadashi Watabe, Shigetoshi Kadota, and Yasuhiro Tezuka;
Sesquiterpenes and Flavonol Glycosides from Zingiber aromaticum and Their CYP3A4 and CYP2D6 Inhibitory Activities;Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630-Sugitani, Toyama 930-0194, Japan.; J. Nat. Prod., 2004, 67 (7), pp 1079–1083; DOI: 10.1021/np030556a; Publication Date (Web): June 17, 2004 (Download Attached PDF Document)
8. Phytochemical discovery of antifeedant, antimicrobial and antirnalarial principles
Semir Omar; University of Ottawa; 2000; (Download Attached PDF Document)
9. 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
10. Clin Pharmacol Ther. 2005 May;77(5):415-26;
In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes; Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah A; Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, 4301 W Markham St, Slot 522, Little Rock, AR 72205, USA; PubMed PMID: 15900287
11. Shufeng Zhou, Hwee-Ling Koh, Yihuai Gao,
Zhi-yuan Gong, Edmund Jon Deoon Lee; Herbal bioactivation: The good, the bad and the ugly; Life Sciences 74 (2004) 935 – 968; April 2003; DOI:10.1016/j.lfs.2003.09.035 (Download Attached PDF Document)
12. J Med Food. 2007 Dec;10(4):643-9.
Pomegranate juice effects on cytochrome P450S expression: in vivo studies. Faria A, Monteiro R, Azevedo I, Calhau C; Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal. PubMed PMID: 18158835
13. Drug Metab Dispos. 2006 Mar;34(3):343-5. Epub 2005 Dec 2.
Transient inhibition of cyp3a in rats by star fruit juice. Hidaka M, Okumura M, Ogikubo T, Kai H, Fujita K, Iwakiri T, Yamasaki K, Setoguchi N, Matsunaga N, Arimori K; Department of Pharmacy, Miyazaki Medical College Hospital, 5200 Kihara, Kiyotake-cho, Miyazaki-gun, 889-1692, Japan; PubMed PMID 16326816
14. Phytomedicine. 2000 Jul;7(4):273-82.
An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT; Ottawa-Carleton Institute of Biology, University of Ottawa, Ontario, Canada. PubMed PMID: 10969720
15. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan.
van Erp NP, Baker SD, Zhao M, Rudek MA, Guchelaar HJ, Nortier JW, Sparreboom A, Gelderblom H. PubMed PMID: 16278402
16. Effect of black seed on dextromethorphan O- and N-demethylation in human liver microsomes and healthy human subjects.
Al-Jenoobi FI, Al-Thukair AA, Abbas FA, Ansari MJ, Alkharfy KM, Al-Mohizea AM, Al-Suwayeh SA, Jamil S. PubMed PMID: 20201775
17. The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9.
Kent UM, Aviram M, Rosenblat M, Hollenberg PF. PubMed: PMID: 12019199
18. CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants.
Usia T, Iwata H, Hiratsuka A, Watabe T, Kadota S, Tezuka Y. PubMed PMID: 16360935
19. Modulation of hepatic drug metabolizing enzymes by dietary doses of thymoquinone in female New Zealand White rabbits.
Elbarbry F, Ragheb A, Marfleet T, Shoker A. PubMed PMID: 22422469
20. Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate.
Yu C, Shin YG, Kosmeder JW, Pezzuto JM, van Breemen RB. PubMed PMID: 12569440
21. The effect of piperine on midazolam plasma concentration in healthy volunteers, a research on the CYP3A-involving metabolism
Mohammad Mahdi Rezaee, Sohrab Kazemi, Mohammad Taghi Kazemi, Saeed Gharooee, Elham Yazdani, Hoda Gharooee, Mohammad Reza Shiran and Ali Akbar Moghadamnia; DARU Journal of Pharmaceutical Sciences 2014 22:8; DOI: 10.1186/2008-2231-22-8
22. Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects.
Robertson SM, Davey RT, Voell J, Formentini E, Alfaro RM, Penzak SR.; Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, New Hampshire Ave., Silver Spring, MD 20901, USA; PMID: 18205997 DOI: 10.1185/030079908X260871
23. Resveratrol Modulates Drug- and Carcinogen-Metabolizing Enzymes in a Healthy Volunteer Study
H-H. Sherry Chow, Linda L. Garland, Chiu-Hsieh Hsu, Donna R. Vining, Wade M. Chew, Jessica A. Miller, Marjorie Perloff, James A. Crowell and David S. Alberts; DOI: 10.1158/1940-6207.CAPR-09-0155 Published September 2010; PubMed PMCID: PMC2933312; NIHMSID: NIHMS207754
24. Clinical Assessment of Botanical Supplementation on Cytochrome P450 Phenotypes in the Elderly: St. John’s wort, Garlic oil, Panax ginseng, and Ginkgo biloba
Bill J. Gurley, PhD., Stephanie F. Gardner, PharmD, EdD., Martha A. Hubbard, MS, D. Keith Williams, PhD., W. Brooks Gentry, MD, Yanyan Cui, PhD, and Catharina Y. W. Ang, PhD.; Drugs Aging. 2005; 22(6): 525–539. PMCID: PMC1858666 [[bibliography]]
25. Repeated administration of berberine inhibits cytochromes P450 in humans
Ying Guo, Yao Chen, Zhi-rong Tan, Curtis D. Klaassen, Hong-hao Zhou; Published online 2011 Aug 26.; Eur J Clin Pharmacol. 2012 Feb; 68(2): 213–217.; doi: 10.1007/s00228-011-1108-2; NIHMSID: NIHMS583946; PMCID: PMC4898966

If an inducer or inhibitor is present on this page and reliable human in vivo studies are available but not shown on this page please leave a comment about it using the Discuss link at the bottom of this page so we can update the inhibitor's data.

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