Kava and caffeine

Quite a lot of people ask us about potential interactions between kava and coffee, or more broadly, caffeine. We are republishing an old (but still valid) post by Jimmy Price, with his blessing.

The issue

People often report that the combination of kava and caffeine produces a noticeable increase in the stimulant effects of caffeine when the two are consumed within a reasonable time of each other. Some people find the combination uncomfortable, others enjoy the lift. Either way, there is a reasonable scientific explanation, and we want to share what we think the culprit is.

How caffeine is metabolised

As noted by scholars:

Caffeine from coffee or other beverages is absorbed by the stomach and small intestine within 45 minutes of ingestion and then distributed throughout all tissues of the body. Caffeine is metabolised in the liver by the cytochrome P450 oxidase enzyme system (specifically, the CYP1A2 isozyme) into three metabolic dimethylxanthines: paraxanthine, theobromine, and theophylline. Paraxanthine increases lipolysis, leading to elevated glycerol and free fatty acid levels in the blood plasma. Theobromine dilates blood vessels and increases urine volume. Theobromine is also the principal alkaloid in cocoa, and therefore chocolate. Theophylline acts on smooth muscle of the bronchi. Each of these caffeine metabolites is further metabolised into various methyluric acids and then excreted in the urine.

References: Lehninger, A.L. (2005) Lehninger principles of biochemistry (4th ed.). New York: W.H Freeman. Salway, J.G. (2004) Metabolism at a glance (3rd ed.). Alden, Mass.: Blackwell Pub.

Kava's effect on metabolic pathways

Kava, much like grapefruit juice, can suppress certain enzyme pathways in the liver, in particular CYP1A2, which is responsible for the majority of caffeine's metabolism. In practical terms this means kava can slow the breakdown of caffeine, lengthening and amplifying its effects until the body finally clears it. Research suggests kava may slow the rate of this metabolism by as much as 56%, which is not negligible. The effect can ripple further as you go down the metabolite tree, since kava inhibits several other commonly used CYP pathways too.

In the present work the inhibition of P450 enzymes by kava extract and individual kavalactones in human liver microsomes (HLMs) was investigated. Whole kava extract (normalised to 100 microM total kavalactones) caused concentration-dependent decreases in P450 activities, with significant inhibition of the activities of CYP1A2 (56% inhibition), 2C9 (92%), 2C19 (86%), 2D6 (73%), 3A4 (78%), and 4A9/11 (65%) following preincubation for 15 min with HLMs and NADPH; CYP2A6, 2C8, and 2E1 activities were unaffected. The activities of CYP2C9, 2C19, 2D6, and 3A4 were also measured after incubation of HLMs with the major kavalactones kawain (K), desmethoxyyangonin (DMY), methysticin (M), and dihydromethysticin (DHM) (each at 10 microM), and NADPH. Whereas K did not inhibit these enzymes, there was significant inhibition of CYP2C9 by DMY (42%), M (58%), and DHM (69%); of 2C19 by DHM (76%); of 2D6 by M (44%); and of 3A4 by DMY (40%), M (27%), and DHM (54%). Consistent with their potency as inhibitors, the two major kavalactones bearing a methylenedioxyphenyl moiety (M and DHM) formed "455 nm" metabolic intermediate complexes after incubation with HLMs and NADPH, but K and DMY did not. [source]

What does this mean for kava drinkers?

When kava drinkers consume coffee, tea, or other caffeinated beverages, they may feel a marked increase in the effects of caffeine: a stronger, more persistent stimulation. Anyone sensitive to caffeine will be even more sensitive and may experience the less pleasant end of the side-effect spectrum, with jitteriness and tension being the most common complaints.

If your morning coffee leaves you jittery and tense after a kava session, you may now have a likely explanation.

So what can I do?

It may seem obvious, but limiting your caffeine intake will limit the increased effects, positive or negative, that you experience. Switch to a less caffeinated brew or to non-caffeinated alternatives, or simply leave a wider gap between your last shell and your next coffee. Many regular kava drinkers find a herbal tea or coconut water serves them better in the morning after a kava session than another strong coffee.

The post was originally published on the kavaforums. Republished on our blog with the blessing of the author.

Related reading

• Best kava chasers: what to reach for between shells
• How to make your evening kava session great
• What is the right amount of kava?
• Kava as an alternative to alcohol

If you're newer to kava, our quick guide for new drinkers is the best place to figure out where to begin.