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Kava Fact of the Day How does kava effect cytochrome P450 enzymes and what does that mean to the daily kava drinker?

The Kap'n

The Groggy Kaptain (40g)
KavaForums Founder
Today’s fact of the day will address kava’s ability to inhibit (reduce function) of various enzymes known as cytochromes.

IC50 Values for Kavalactones at Isoforms.jpg

Cytochrome P450, also known as CYPs, are a family of enzymes that oxidize (break down) about 75-80% of all drugs in the body. These are important in the world of kava because kava, kava extract, and individual kavalactones have been shown in several studies to inhibit these enzymes to different degrees. When these enzymes are inhibited, whatever chemical which used that enzyme to metabolize will be slowed in its elimination, or at least in theory based on these papers.

Most of the work today resides in the image attached. Attached is my attempt at taking these three studies and producing their results in a readable format. We’re using what’s known as IC50 values to denote the strength of inhibition of kava and fractions of kava. IC50 is defined as: a measure of the potency of a substance in inhibiting a specific biological or biochemical function [7]. Quite a number of natural products can inhibit these enzymes including grapefruit juice. In the attached diagram we see the reference values for grapefruit highlighted in yellow. These are the inhibition values you would see if you consumed grapefruit juice instead of kava. It’s worth it to note the inhibition values of grapefruit are much stronger than those of kava. The main two enzymes used in the vast bulk of elimination of pharmaceutical drugs are the enzymes CYP2D6 and CYP3A4. CYP2D6 was thought to be inhibited by kava, however these studies provide evidence that shows this may not be the case. CYP3A4, which accounts for roughly half of all drug metabolism has indeed shown inhibition in the presence of kava, and kava fractions.

What this means to the average kava drinker is that if you consume kava daily, you may want to watch out for pharmaceutical drugs which caution against the concurrent consumption of grapefruit juice. This warning is almost always printed on the side of the bottle. While kava may not be as strong of an inhibitor at these sites, it stands to reason that the compounding effect of consuming kava daily may indeed cause these inhibitory effects. This can cause these specific drugs to stay in your system for longer periods than intended, or cause their metabolites to stay in a specific form for a longer amount of time. Either of which, depending on the drug, can be benign or problematic.



[1] Anke J, Ramzan I. Pharmacokinetic and pharmacodynamic drug interactions with Kava (Piper methysticum Forst. f.). J Ethnopharmacol. 2004 Aug;93(2-3):153-60. doi: 10.1016/j.jep.2004.04.009. PMID: 15234747.

[2] Zou L, Harkey MR, Henderson GL. Effects of herbal components on cDNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci. 2002 Aug 16;71(13):1579-89. doi: 10.1016/s0024-3205(02)01913-6. PMID: 12127912.

[3] Gurley BJ, Swain A, Hubbard MA, Williams DK, Barone G, Hartsfield F, Tong Y, Carrier DJ, Cheboyina S, Battu SK. Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res. 2008 Jul;52(7):755-63. doi: 10.1002/mnfr.200600300. PMID: 18214849; PMCID: PMC2562884.

[4] Côté CS, Kor C, Cohen J, Auclair K. Composition and biological activity of traditional and commercial kava extracts. Biochem Biophys Res Commun. 2004 Sep 10;322(1):147-52. doi: 10.1016/j.bbrc.2004.07.093. PMID: 15313185.

[5] Ogliaro F, de Visser SP, Cohen S, Sharma PK, Shaik S. Searching for the second oxidant in the catalytic cycle of cytochrome P450: a theoretical investigation of the iron(III)-hydroperoxo species and its epoxidation pathways. J Am Chem Soc. 2002 Mar 20;124(11):2806-17. doi: 10.1021/ja0171963. PMID: 11890833.

[6] L. Zou, G. L. Henderson, M. R. Harkey, Y. Sakai, & A. Li2. (2004). Effects of Kava (Kava-kava, ‘Awa, Yaqona, Piper methysticum) on c-DNA-expressed cytochrome P450 enzymes and human cryopreserved hepatocytes. Phytomedicine, 11(4), 285–294.

[7] Ic50. (2021, January 08). Retrieved April 05, 2021, from https://en.wikipedia.org/wiki/IC50
 
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