I don't think an antihistamine is the answer. I too have noticed this rash. I've been trying to figure it out for about a year now and have left many posts on this forum about my hypotheses from my research. Ethanol is metabolized by ethanol dehydrogenase and CYP 2E1 to make acetaldehyde, which is then metabolized by acetaldehyde dehydrogenase (ALDH2) to form acetate. First of all, I speculate that kava inhibits acetaldehyde dehydrogenase 2, if not many isoforms of this family of proteins. I think this leads to the build up of acetaldehyde in the system and the classic acetaldehyde toxicity rash (warm/hot, reddened face, neck and splotchy, spotted rash around the shoulders and chest and back, shallow breathing, headache, ocular pressure). If you had the genetic mutation ALDH2 *2 allele, one each from your mom and dad (homozygous, common in Asian ethnicity) then this rash reaction would occur anytime you drank a beer. The *2 mutation causes the ALDH enzyme not to work properly, therefore the buildup of acetaldehyde. Here's the catch, it doesn't happen all the time, as you have stated. This is because your ALDH2 gene does not have this *2 mutation, and even if you did have this mutation you could just be heterozygous (one normal copy and one *2), which is not as big a deal but can affect my hypothesis when combined with kava. There are quite a few known chemical inhibitors of ALDH2, and I think kava is obviously a reversible inhibitor. As stated in this thread, the drug disulfiram (Antabuse) is an ALDH2 inhibitor, and it causes this same reaction. What do you do when you see this reaction after having a beer? You don't drink anymore. It works, and kava does the same thing. The key to all this madness could be genetic, but could also be as simple as your diet. Research has shown that inducers of ALDH2 activity are found in cruciferous vegetables of the Brassicaceae family. Those food include cauliflower, cabbage, garden cress, bok choy, broccoli, Brussels sprouts and similar green leaf vegetables. Two of the known compounds are the anti-oxidants alpha-lipoic acid (of which you can buy in supplement form) and BITC (rich in papaya, a member of the isothiocyanates in cruciferous veggies). I eat a lot of cruciferous foods with dinner and I rarely have this rash, but when I do get it (rarely) if I am enjoying a beer after a nice Squanch session I have noted that my diet was low in cruciferous veggies. If my hypothesis is correct, if you eat a lot of cruciferous vegetables prior to drinking kava, and then you drink a beer or two, you should not get this acetaldehyde reaction rash. I'm sure there are plenty of other foods that could affect this. Keep a record of what you ate that day when you have the rash. You could also try taking the alpha-lipoic acid supplement prior to drinking kava. Now I know there is a lot of different types of protein inhibition binding, competition for binding sites, allosteric regulation, possibly an inhibitor preventing an inducer from binding or working based on conformational shapes of the active or inactive protein, but I am quite certain that diet plays a role in the randomness of this acetaldehyde reaction. If I had funding to do it, it would be easy to research in the lab both in vitro and cell culture. But I don't and I am not in a lab anymore, so I wish someone out there would research this. Anyway, if you add in a heterozygous ALDH *2 mutation (one normal and one mutated) on top of the kava, the rash could happen more often and more severely, without diet affecting it. Other mutations such as poor metabolism for CYP2E1 and possibly ethanol dehydrogenase could also play into this. We know kava inhibits 2E1 and it could also inhibit ethanol dehase, which would explain the higher sensitivity to the effects of alcohol (the reported synergy). But the rash has to be more downstream at the acetaldehyde level. Experiment. PM me if you figure anything out! It for sure is interesting. The best thing is to just keep the alcohol to a minimum when drinking kava. If you do happen to have a beer after kava and you feel warmth to your face, poor it down the drain. Most likely you are experiencing the early effects of building acetaldehyde prior to the rash. All of this is not proven and pure speculation based on my observations and literature research. BULA!
