The cytochrome P450 enzyme CYP2E1 occurs in many parts of the human body (skin, nose, heart, brain, lung, liver, kidney etc.), but is most concentrated in the human liver. It makes up only about 7% of the total P450 enzymes in the liver.[15]

CYP2E1 accounts for approximately 7% of total CYP450 in the human liver.

Many sulphur-containing agents block this enzyme, such as carbon disulphide, diethyldithiocarbamate, and disulfiram.[15]

Enzyme Actions

1'-Hydroxylation of Allylbenzenes

Unlike many other cytochrome P450 enzymes, CYP2E1 appears to only catalyze 1'-hydroxylation, without also catalyzing O-demethylation or O-demethylenation. For this reason, it could possibly be the single most important cytochrome P450 enzyme to induce to help achieve oilahuasca activation.

CYP2E1 and CYP1A2 can each catalyze the metabolism of methyl eugenol to 1'-hydroxymethyleugenol.

methyl eugenol CYP2E1 + CYP1A2 1'-hydroxymethyleugenol
methyl-eugenol.gif —-> 1-Hydroxymethyleugenol.png

CYP2E1, and to a lesser degree CYP2C9, can each catalyze the metabolism of safrole to 1'-hydroxysafrole.

safrole CYP2E1 + CYP2C9 1'-hydroxysafrole
safrole.gif —-> 1-hydroxysafrole.png

The alcohol 1'-hydroxyestragole is proven to be created from the allylbenzene methyl chavicol in human liver in vitro primarily by the P450 enzymes CYP1A2, CYP2A6 and CYP2E1.[20][21]

methyl chavicol CYP2E1 1'-hydroxyestragole
methyl_chavicol.png —-> 1-hydroxyestragole.png

Action on Ketones

CYP2E1 oxidizes several ketones include acetone, methyl ethyl ketone, and methyl isobutyl ketone.[15] Acetone is a potent inducer of CYP2E1.[15]

CYP2E1 is involved in the conversion of acetone to acetol in mice.[13]

acetone CYP2E1 acetol
acetone.png —-> acetol.png

Creation of Aldehydes

CYP2E1 catalyzes the metabolism of ethanol to acetaldehyde. In this reaction, CYP2E1 initially forms a very unstable gem-diol, known as 1,1-ethanediol, which then condenses to form acetaldehyde.

Ethanol CYP2E1 1,1-Ethanediol Condensation Acetaldehyde
Ethanol.png -> 1_1-Ethanediol.png -> Acetaldehyde.png

CYP2E1 catalyzes the metabolism of propargyl alcohol to propiolaldehyde.

propargyl alcohol CYP2E1 propiolaldehyde
propargyl-alcohol.png —-> propiolaldehyde.png

Oxygen Double Bond Creation

CYP2E1 catalyzes the metabolism of acetaminophen to N-acetyl-4-benzoquinoneimine.

acetaminophen CYP2E1 N-acetyl-4-benzoquinoneimine
Acetaminophen.png —-> N-acetyl-4-benzoquinoneimine.png

Epoxide Creation

CYP2E1 is involved in many epoxidation reactions. CYP2E1 epoxidates acrylamide into glycidamide[14], acrylonitrile into 2-cyanoethylene oxide, and benzene to benzene oxide. CYP2E1 and CYP1A2 together epoxidize styrene to styrene oxide. CYP2E1 together with CYP1A2 and CYP3A4 epoxidates trans-phenylpropylene (propenylbenzene) to it’s epoxide.

Inhibitors of CYP2E1

CYP2E1 is easily inhibited. Common foods such as garlic and watercress are proven to inhibit CYP2E1 in humans.

Potent Inhibitors Strength Dosage Verified in Humans
Bergamot EO ? ? ?
Cinnamaldehyde ? ? ?
Cinnamon (contains o-methoxycinnamaldehyde) ? ? ?
Cinnamon EO1 ? 5-10 drops (Unverified) ?
Disulfiram [12] ? 500 mg Yes
Genistein [22] ? ? ?
Grapefruit EO ? ? ?
Kaempferol 60–88% inhibition[27] ? ?
Lemon EO ? ? ?
Lime EO ? ? ?
Neroli EO ? ? ?
O-methoxycinnamaldehyde[25] (found in cinnamon) ? ? ?
Orange EO ? ? ?
Petitgrain EO ? ? ?
Resveratrol ? 500 mg once daily for 10 days Yes[26]
Saint John’s Wort2 [7] 100% High doses ?
Star fruit juice ? ? ?
Tangerine EO ? ? ?
Tannic acid ? ? ?
Watercress 56% increase in substrates 50 grams of fresh watercress Yes[19]
Moderate Inhibitors Strength Dosage Verified in Humans
Moderate Inhibitors ? ? ?
Diallyl sulfide (found in garlic) 31% inhibition 0.2 mg/kg Yes[18]
Garlic EO [2] 39% inhibition ? Yes[2]
Horse Chestnut [7] 30% inhibition 4.9 mM ? ?
Kava [3] 40% inhibition ? Yes[3]
Mandarin EO ? ? ?
Piperine Inhibition 20 mg for 10 days Yes[28]
Safrole ? ? ?
Weak Inhibitors Strength Dosage Verified in Humans
Cone Flower [7] 10% inhibition 4.7 mM ? ?
Curcumin ? ? ?
Ginkgo biloba [7] 20% inhibition 2.2 mM ?
Valerian Root [7] 10% inhibition 18.8 mM ? ?
Myricetin ? ? ?
Sage [7] 10% inhibition 8.2 mM ? ?
Turmeric ? ? ?
Inhibitors of Unknown Potency Strength Dosage Verified in Humans
Acai berry oil ? ? ?
Bergamottin ? ? ?
Citral (geranial/neral) ? ? ?
Dimethyl sulfoxide (DMSO)3 ? ? ?
Ellagic Acid ? ? ?
Garlic ? ? ?
Lemongrass EO ? ? ?
Limonene ? ? ?
Naringin ? ? ?
Pomegranate juice [11] ? ? In mice only
Pomegranate leaf ? ? ?
Propylene glycol ? ? ?
Quercetin ? ? ?
Silymarin ? ? ?
In Vitro Inhibitors Ineffective in Humans Strength Dosage Verified in Humans
Goldenseal extract4 No Effect[3] ? Yes
White Grapefruit No Effect[16] 1-2 cups Yes

Note: Piperine was previously in this list because it was shown to inhibit CYP2E1 by 30% in rats[6], however it was removed because another test using human liver found that piperine has almost no effect on CYP2E1.[23]

Inducers of CYP2E1

CYP2E1 appears to be easily and rapidly induced. In rats in vivo myristicin induced CYP1A1, CYP1A2, CYP2B1, CYP2B2, and CYP2E1. Maximum induction was at 12 hours for CYP2E1 and 24 hours for the other enzymes.[24] Glycerin showed a 250% to 300% increase of CYP2E1 in vitro after only 4-8 hours.[4]

Potent Inducers Strength Dosage Verified in Humans
Acetone ? ? Yes
Alcohol [10] 5-10x increase [15] ? Yes
Glycerin [17][4] 2.5x to 3x increase in vitro after 4-8 hours [4] ? ?
Phenobarbital[8] ? ? ?
Saint John’s Wort5 30-65% Induction 900mg Yes
Moderate Inducers Strength Dosage Verified in Humans
Rifampicin [7] ? ? ?
Inducers of Unknown Potency Strength Dosage Verified in Humans
Acetaldehyde [10] ? ? ?
Alpha-Naphthoflavone ? ? ?
Benzene [10] ? ? ?
1,3-Butandiol [10] ? ? ?
n-Butanol [10] ? ? ?
Capsaicin [1]6 ? ? ?
Cayenne pepper (contains Capsaicin)7 ? ? ?
Diethylether [10] ? ? ?
Dihidrocapsaicin [1] ? ? ?
Dimethyl sulfoxide (DMSO)8 ? ? ?
3-Hydroxypyridine [10] ? ? ?
Imidazole [10] ? ? ?
Isoniazid [10] ? ? ?
Isopropanol ? ? ?
Ketoconazole [10] ? ? ?
4-Methylpyrazole [10] ? ? ?
Myristicin ? ? ?
2-Propanol [10] ? ? ?
Pyridine ? ? ?
Pyrazine [10] ? ? ?
Pyrazole [10] ? ? ?
Pyrimidine [10] ? ? ?
Sage [5]9 ? ? ?
Skatole ? ? ?
Thiazole [10] ? ? ?
Thrichloroethylene [10] ? ? ?
Triazole [10] ? ? ?
m-Xylene [10] ? ? ?
o-Xylene [10] ? ? ?
p-Xylene [10] ? ? ?
1. J Asian Nat Prod Res. 2012;14(4):382-95. doi: 10.1080/10286020.2012.656605.
Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo. Zhang QH, Hu JP, Wang BL, Li Y. Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Materia Medica, Beijing 100050, China; PubMed PMID: 22375877
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
3. 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
4. Yang MX, Cederbaum AI.
Glycerol increases content and activity of human cytochrome P-4502E1 in a transduced HepG2 cell line by protein stabilization. Alcohol Clin Exp Res. 1997 Apr;21(2):340-7.; Department of Biochemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.
5. Lima CF, Fernandes-Ferreira M, Pereira-Wilson C.;
Drinking of Salvia officinalis tea increases CCl(4)-induced hepatotoxicity in mice; Food Chem Toxicol. 2007 Mar;45(3):456-64. Epub 2006 Oct 1. Department/Centre of Biology, School of Sciences, University of Minho, 4710-057 Braga, Portugal.
6. Xenobiotica. 1994 Dec;24(12):1195-204;
Piperine effects on the expression of P4502E1, P4502B and P4501A in rat; Kang MH, Won SM, Park SS, Kim SG, Novak RF, Kim ND.; College of Pharmacy, Seoul National University, Korea; PubMed PMID: 7771106
7. Basic Clin Pharmacol Toxicol. 2009 Jul;105(1):58-63. doi: 10.1111/j.1742-7843.2009.00412.x. Epub 2009 Apr 3;
Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes; Hellum BH, Hu Z, Nilsen OG; Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; PubMed PMID: 19371257 (Download Attached PDF Document)
8. J Biochem Mol Toxicol. 2005;19(6):368-78;
Quantification of the expression and inducibility of 12 rat cytochrome P450 isoforms by quantitative RT-PCR; Caron E, Rioux N, Nicolas O, Lebel-Talbot H, Hamelin BA; Department of Pharmacology and Toxicology, Shire-Biochem Inc., Laval, Quebec, Canada. PubMed PMID: 16421897
9. Katsunori Yamaura, Maki Shimada, Noriyuki Nakayama, Koichi Ueno;
Protective effects of goldenseal (Hydrastis canadensis L.) on acetaminophen-induced hepatotoxicity through inhibition of CYP2E1 in rats; PubMed PMID: 22224048
10. Costas Ioannides;
Cytochromes P450: Metabolic & Toxicological Aspects; CRC Press, 1996; ISBN 0849392241, 9780849392245
11. 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
12. J Pharmacol Exp Ther. 1999 Oct;291(1):213-9.
Duration of cytochrome P-450 2E1 (CYP2E1) inhibition and estimation of functional CYP2E1 enzyme half-life after single-dose disulfiram administration in humans. Emery MG, Jubert C, Thummel KE, Kharasch ED; Department of Pharmaceutics, Anesthesiology Service, Puget Sound Veterans Affairs Medical Center, Seattle, Washington, USA. PubMed PMID: []
13. Biochem Pharmacol. 1999 Aug 1;58(3):461-3.
Acetone catabolism by cytochrome P450 2E1: studies with CYP2E1-null mice. Bondoc FY, Bao Z, Hu WY, Gonzalez FJ, Wang Y, Yang CS, Hong JY; Laboratory for Cancer Research, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway 08854-8020, USA; PubMed PMID: 10424765
14. Arch Toxicol. 2008 Oct;82(10):717-27. doi: 10.1007/s00204-008-0296-8. Epub 2008 Apr 17.
Human CYP2E1 mediates the formation of glycidamide from acrylamide. Settels E, Bernauer U, Palavinskas R, Klaffke HS, Gundert-Remy U, Appel KE; Center for Experimental Toxicology, Federal Institute for Risk Assessment, Thielallee 88-92, 14195 Berlin, Germany. PubMed PMID: 18418580
15. Human Drug Metabolism: An Introduction
Michael D. Coleman; John Wiley & Sons, 2010; ISBN 047068934X, 9780470689349
16. 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
17. Effects of Purified Glycerol from Biodiesel on Cyp1a1 and Cyp2e1 Expressions in CBA/CA Mice
Szele E, Gombos K, Kovács A, Ember I.; In Vivo. 2011 Mar-Apr;25(2):237-40.; PMID: 21471540
18. The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone.
Loizou GD, Cocker J.; Hum Exp Toxicol. 2001 Jul;20(7):321-7.; PMID: 11530830
19. Inhibition of chlorzoxazone metabolism, a clinical probe for CYP2E1, by a single ingestion of watercress.
Clin Pharmacol Ther. 1998 Aug;64(2):144-9.; Leclercq I, Desager JP, Horsmans Y.; PMID: 9728894 DOI: 10.1016/S0009-9236(98)90147-3
20. Douglas W. Bristol, Ph.D., Study Scientist
NTP Technical Report on the 3-Month Toxicity Studies of Estragole; National Toxicology Program, Toxicity Report Series, Number 82; NIH Publication No. 11-5966; National Institutes of Health, Public Health Service, U.S. Department of Health and Human Services Download Attached PDF Document
21. Evaluation of human interindividual variation in bioactivation of estragole using physiologically based biokinetic modeling.
Punt A, Jeurissen SM, Boersma MG, Delatour T, Scholz G, Schilter B, van Bladeren PJ, Rietjens IM. PubMed: 19920071
22. Protective effect of genistein isolated from Hydrocotyle sibthorpioides on hepatic injury and fibrosis induced by chronic alcohol in rats.
Huang Q, Huang R, Zhang S, Lin J, Wei L, He M, Zhuo L, Lin X.; Toxicol Lett. 2013 Feb 27;217(2):102-10. doi: 10.1016/j.toxlet.2012.12.014. Epub 2012 Dec 26.; PMID: 23274713 DOI: 10.1016/j.toxlet.2012.12.014
23. Curcuminoids inhibit multiple human cytochromes P450 (CYP), UDP-glucuronosyltransferase (UGT), and sulfotransferase (SULT) enzymes, while piperine is a relatively selective CYP3A4 inhibitor
Laurie P. Volak, Senait Ghirmai, John R. Cashman, and Michael H. Court PubMed PMC ID: PMC2574793
24. Biochem Biophys Res Commun. 1995 Dec 26;217(3):966-71.
Induction of rat hepatic cytochrome P450 enzymes by myristicin. Jeong HG, Yun CH; Department of Environmental Science, Chosun University, Kwangju, Korea. PubMed PMID 8554622
25. Identification of inhibitory component in cinnamon—O-methoxycinnamaldehyde inhibits CYP1A2 and CYP2E1-.
Hasegawa A, Yoshino M, Nakamura H, Ishii I, Watanabe T, Kiuchi M, Ishikawa T, Ohmori S, Kitada M.; Drug Metab Pharmacokinet. 2002;17(3):229-36. PMID: 15618674
26. Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in Healthy Human Volunteers.
Bedada SK, Neerati P.; Phytother Res. 2016 Mar;30(3):463-8. doi: 10.1002/ptr.5549. Epub 2015 Dec 17.; PMID: 26680654; DOI: 10.1002/ptr.5549
27. Protective Effects of Kaempferol on Isoniazid- and Rifampicin-Induced Hepatotoxicity
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28. Effect of piperine on CYP2E1 enzyme activity of chlorzoxazone in healthy volunteers.
Bedada SK, Boga PK. Xenobiotica. 2016 Sep 27:1-25. PMID: 27670974; DOI: 10.1080/00498254.2016.1241450

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