1 Reply by woefullysober

(32 replies, posted in Focused Discussion)

I was not aware of Convivia. I have to admit, it's clever. Recycling an already approved drug for another purpose is certainly one way to fast-track to the market. It looks like they've already completed a phase IIa trial, although it was way back in 2008 and I can't seem to find anything more recent. (I wonder what in the world they have been doing since then.) Here's the link to the actual trial in case you're interested. Unfortunately they don't post any hard results.
(I can't post links for some reason so go to clinicaltrials . gov and search "4-methylpyrazole aldh2")

The problem I see with this drug is liability. It's an interesting idea. In us, acetaldehyde dehydrogenase (coded by ALDH2) is the bottleneck of alcohol metabolism, so acetaldehyde builds up. This Convivia slows down the first step in the reaction, the conversion of alcohol to acetaldehyde, presumably just enough so that our defective acetaldehyde dehydrogenase can keep up with all the newly forming acetaldehyde being thrown at it. The problem is, this would theoretically shift the bottleneck to the first step, meaning instead of a buildup of acetaldehyde, alcohol itself would build up. Yes, this would definitely lower the levels of the carcinogenic acetaldehyde, but it would create a potentially dangerous inability to metabolize alcohol itself. Meaning whoever took it would probably get drunk very easily, and if they weren't careful, could do themselves serious harm from outright alcohol intoxication. Basically, it could lower your liquor tolerance to that of a, we'll say, 10 year old girl.

Maybe they can work out a final dosage that finds a happy balance between slowing down the alcohol dehydrogenase just enough to keep our defective acetaldehyde dehydrogenase from overloading, but keeping the alcohol dehydrogenase fast enough so that we don't black out after a couple beers. But even then, I think at the very least it's playing with fire, and I'm a little surprised this actually took off. You're seriously going to rely on people to be rational and not "overdo it" as they partake in what may be the most singular, fool-proof, time-tested catalyst for irrational behavior known to humankind? Yes, people exercise restraint all the time when drinking alcohol, but bars and grocery stores don't get sued when someone drinks themself to death or kills someone while running a red light. Call me morbid, but what I see from this is some story in the Sunday paper about a freshman being found dead in his dorm room with a bottle of this stuff next to his bed. Drug companies don't want to deal with that. At least none that I know of, but maybe (probably) Raptor knows something I don't.

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2 Reply by woefullysober

(32 replies, posted in Focused Discussion)

Hi. Let me add some more disheartening accounts to this list. I've tried NAC twice now. Both times failed miserably.

Some background. I've been abstinent for years. Experimented quite a bit in college but ultimately decided it just wasn't worth it. If I didn't drink often, my tolerance would wane quickly and I would throw up after drinking a single beer. I tended to tolerate equivalent amounts of alcohol in hard liquor a bit better. I have a background in biology and this NAC idea seemed intriguing from a "biochemical" perspective, so like the rest of you I gave it a try.

The first time I took all of these at once about 30 min after eating and about 45 min before drinking a beer (5.5% alcohol):
5 pills of Jarrow NAC sustain (600mg x5 = 3g)
6 capsules of LifeExtension "Anti-Alcohol antioxidants" (6 capsules = total of 1200mg NAC, 3g Vit C. Also contains 100mg B1 and 50mg glutathione, among other things)
Results: Took about 30 min of drinking before the flush came on. By around 45 min I had finished about 3/4 of a pint. My heart was racing in the 120s, I was hot and red, and I was beginning to feel nauseous. Sleepiness and a headache soon followed.

The second time I doubled the dosage and waited 90 min before consuming the alcohol:
10 pills of Jarrow NAC = 6g NAC
12 capsules of LifeExtension = 2.4g NAC and 6g Vit C
Results: Essentially the same. Still got hot and red, the racing heart. But it was all very slightly more tolerable. This could easily have been just how I was feeling that day, or I could have been imagining the difference. The only objective evidence I had was that my heart rate only reached the 110s this time and I did not get nauseous, but I still felt ill enough that I couldn't finish the remaining 1/4 pint of beer. And yes, I was gassy and my farts smelled god-awful.

As an aside, after taking the total of 8.4g of NAC the second time without really thinking about it, I briefly freaked out that I could have overdosed myself. A quick search revealed that you can indeed overdose on NAC. There are case reports of accidental infusions in hospitals. It's primarily used to treat Tylenol overdose, and the loading dose (the dose needed to reach a therapeutic level) is 150mg/kg, which for a 60kg little Asian person is 9g of NAC. Very close to what I took. In the few case reports of overdoses, the patients were given well over 100g, doses that led to brain swelling, seizures, and even death. Where does NAC become toxic between the say ~10g loading dose and the huge doses these people were given? I don't think anybody knows. So be careful out there folks.

In any case, I think I'm done experimenting for a long time. The most hopeful and scientifically sound prospect by far appears to be this alda-1. But there are still so many barriers to the development of an "Asian glow pill." If I let my imagination run wild, I could see something like this in maybe 10 years at the earliest. In my heart of hearts though, I seriously doubt this will ever come to fruition, and here's why:

1. The initial research just used alda-1 as a proof-of-concept for an entire class of new drugs that could work similarly- more a stepping stone than a finished product.
2. The major therapeutic aim is not for the benefit of socially inhibited Asians; it is for reducing damage from prolonged treatment with nitroglycerin during a heart attack, which I can tell you is important but not that big of a deal. The research into ALDH2 deficiency and Alzheimer's and Parkinson's disease actually seems a lot more potentially relevant.
3. Despite all this, we don't even have evidence yet that this will work at at all in humans (as opposed to rats).
4. If it does work, the dosages for these heart attack patients might be completely different from what would be needed for say a night on the town.
5. Not to mention that nobody knows much about toxicities either.
6. There are so many missteps in the clinical trials process that could easily doom drugs. Most drugs have several clinical trials of similar acting drugs and only a few make it to market. There is only one version of this drug, so the odds are even lower.
7. Finally, the ethical considerations of manufacturing and marketing a drug that could potentially introduce alcoholism to hundreds of millions of people means that an "Asian glow pill," one that is designed specifically for this purpose with correct dosages that can be prescribed by a doctor like any other medicine, will probably always remain a pipe dream even if the science behind it becomes a reality.
8. Then again, with the money that could be had from such a pill, you never know these days. Still, I'm once again putting this fantasy back to rest. Maybe I'll check in again in 10 years, but in the meantime I'll be getting on with my life without alcohol.

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