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Alcohol Alcohol Megathread

A CYP2E1 inhibitor could be of benefit, especially with chronic drinking.
Also it looks like zinc supplementation is part of it, to reduce ROS and lipid peroxidation. Although ADH produces acetaldehyde, I will see what kind of inhibitors could work for both of these and look into what the alternate metabolism pathway would be.

Suppression of ROS Generation
ADH is the major enzyme responsible for alcohol metabolism in the liver, at normal physiological condition. However, chronic alcohol consumption induces cytochrome P450 2E1 (CYP2E1), instead of ADH.112,113 Alcohol metabolism via CYP2E1 pathway generates ROS, and it has been well defined that hepatic CYP2E1 induction represents a major mechanism for alcohol-induced oxidative stress.114 Zinc is a cofactor of ADH, and removal of zinc from ADH led to a complete loss of its catalytic activity.8 In alcoholic patients, a significant reduction of hepatic ADH activity is associated with zinc decrease in the liver.115 Thus, alcohol-induced hepatic zinc depletion is most likely linked to a shift of alcohol metabolic pathway from ADH to CYP2E1 that favors ROS generation. Indeed, dietary supplementation with zinc sulfate suppressed alcohol-elevated CYP2E1 activity, while it increased ADH activity in the liver of alcohol-fed mice.26 Meanwhile, the accumulation of ROS and lipid peroxidation products, including 4-HNE and MDA, in the liver was also attenuated by zinc supplementation.
 
OMG, a gallon of wine and speed would completely destroy my stomach (and eventually kill me)! And I'm not saying that to be judgmental because I've been there before, and it wasn't pretty. I wouldn't go cold-turkey from that, but at least try to taper down the best you can.

I think it's just the fact that alcohol is so profoundly disinhibiting. If I tried to just buy a 6 pack, for example, when I finished that the urge to keep drinking was completely overwhelming and uncontrollable. Even with benzos I could call it a night, but not with alcohol. That and the fact that you can't really buy an odd number of beers/wine/liquor. It's a 6, 12 or 24 pack... or 1,2,3 bottles of wine or a full bottle of liquor. Hard to buy a 12 pack and just drink 9 if you get what I mean.

I know exactly what you mean. I would always say things like, "Okay, I'll buy a 6-pack but I'll only drink 3 and save 3 for tomorrow". Yeah, right! :rolleyes:
 
This article shows how some phenols can inhibit alcohol dehydrogenase and lower blood acetaldehyde levels.

You can also find some promising inhibitors on this page. http://herbpedia.wikidot.com/alcohol-dehydrogenase

I did a test with about 75mg vanillin and some red wine. It is definitely a smoother experience, no headache feeling at all. Just the feeling of dehydration which is easily accomodated.

The ideal stack would include an ADH inhibitor and an ALDH inducer.
 
I'm not that much familiar with the subject, but I would suggest you to look at molybdenum. Ethanol turns into acetaldehyde, which is toxic, and molybdenum is essential to turn acetaldehyde into acetic acid, that the body can excrete.
 
Thanks for your addition! Molybdemium must be a cofactor for the ALDH enzyme (aldehyde dehydrogenase).
 
I recently read about some study out of Finland that showed that a certain supplement the name of which currently escapes me eliminated hangovers in their test subjects.

It was a fairly well-known supplement used in post-workout recovery, I believe it was.

Personally, I find that throwing in some mushroom tea near the end of a drinking session eliminates the worst of the hangover effects the next day (including complete elimination of headache). Not quite what you were looking for, I know.
 
what about actylecystine? (NAC).
NAC is a glutathione precursor, but I'm not sure how efficient it is, it may be more effective if you inject it.

Ethanol metabolism depletes glutathione, which is the main biological antioxidant and it's also involved in many (major) enzymatic reactions.
Glutathione can be in 2 forms: GSH which is normal or reduced glutathione, and GSSG which is glutathione disulfide or oxidized glutathione. There's a very delicate balance between the 2.
When there isn't enough GSH, the cells are more exposed to free radical (or ROS) damage.

And yeah if you could inhibit ADH (alcohol dehydrogenase) and/or induce ALDH, that would prevent most of the damage caused by acetaldehyde, at least in theory. I have not researched this enough but my intuition tells me it may be a tricky thing to do, without messing with other enzymes and stuff. And how would the body compensate for acute inhibition/induction of said enzymes?
But I've thought about it as well, will look at the current literature when I have the time.

About CYP2E1, it does intervene in ethanol metabolism but AFAIK it plays a fairly minor role. Could be a potential target though, but that wouldn't prevent the damage from acetaldehyde.
 
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NAC is a glutathione precursor, but I'm not sure how efficient it is, it may be more effective if you inject it.

Ethanol metabolism depletes glutathione, which is the main biological antioxidant and it's also involved in many (major) enzymatic reactions.
Glutathione can be in 2 forms: GSH which is normal or reduced glutathione, and GSSG which is glutathione disulfide or oxidized glutathione. There's a very delicate balance between the 2.
When there isn't enough GSH, the cells are more exposed to free radical (or ROS) damage.

And yeah if you could inhibit ADH (alcohol dehydrogenase) and/or induce ALDH, that would prevent most of the damage caused by acetaldehyde, at least in theory. I have not researched this enough but my intuition tells me it may be a tricky thing to do, without messing with other enzymes and stuff. And how would the body compensate for acute inhibition/induction of said enzymes?
But I've thought about it as well, will look at the current literature when I have the time.

About CYP2E1, it does intervene in ethanol metabolism but AFAIK it plays a fairly minor role. Could be a potential target though, but that wouldn't prevent the damage from acetaldehyde.
fomepizole and zinc? and maybe some homotaurine.
 
Hi all, first time poster. Just a quick question. I know you all aren't doctors and everybody's bodies react differently. But I'm 31 and I was pretty much mostly a Thursday-Saturday drinker throughout my 20s and I still pretty much stick to those days and have zero alcohol any other days unless its a special occasion. My intake is usually about 8 light beers or so and a couple shots of fireball on Thursdays. And on Fridays and Saturdays id say I consume probably 10-12 light beers and 2-3 shots each night. So roughly 40 drinks a week. I never really drank that much at home until quarantine, used to be mostly at bars.

Let me also say I workout 5 days a week and have for years, also take vitamins and supplements, drink a lot of water, and for the most part watch what I eat during the week. What are your thoughts for my long term health outlook? I feel fine right now but I tend to be a hypochondriac and worry about long term health effects of everything. But im really not interested in quitting drinking, it relaxes me and there's not much else to do where I live, everyone seems to drink a decent amount. Thoughts?
 
The bad news is that 40 drinks a week is a lot and definitely considerably more than I would recommend for a healthy lifestyle.

The good news is that with alcohol, your body will usually let you know when you're drinking too much and if you listen to your body and slow down/stop when it tells you to, you will probably be fine.

I would recommend you try moving from drinking every weekend to every other weekend. Giving your body an extra week without alcohol will do wonders for you long term and also make it easier to quit completely if you decide to. Spend the alcohol free weekend immersing yourself in other hobbies/interests. As long as you can find something else you enjoy doing, you won't even miss alcohol that much.
 
That is a large amount, although in my country (Chile) that amount is what more than half of the population drinks, if not more hahahha.

Haven't you had routine medical exams lately? How have they come out?

I am also curious to know if with that amount of alcohol do you keep kinda in shape? or do you have a beer barrel? Hahaha. I have never liked to drink for that, in large part, the calories thing.
 
Just confirming again, vanillin works very well for hangover removal, I really never want to drink without it now. I think the dosage I am eyeing out is actually more around the 500 mg range. I have a scale but I still havn't measured it out exactly. Vanillin just by itself greatly increases wellbeing and totally removes the headache during and after drinking. I am suprised that there hasn't been a huge potentiation and increase in duration because of the ADH inhibition. It may be present in a small extent but it's definitely not super prominent. There must be a good amount of other metabolism enzymes at play.

I have also been using a multimineral that includes a solid dose of molybdenum and zinc. I'm using 2+ grams of KCl to keep electrolytes up. Drinking lots of water. And a multivitamin with more antioxidants, B vitamins etc. which seems to help extend the protection and keeps the experience smooth. The comedown brings me right back to baseline, with energy to spare! It's really amazing! No negative feelings whatsoever. Sleep afterwards is sometimes a little difficult, the ethanol withdraw kinda has an upper type effect for me. So melatonin is helpful in that case.

Magnesium supplements help with glutamate protection, which I believe is part of ethanol withdraw. Sometimes I also use an ashwaganda extract that has 20 mg piperine (piperine is also an ADH inhibitor)

Drinking red wine helps of course, because of the polyphenols.

Glutathione is definitely important like you guys mentioned above. But I take some great supplements that help with that, so it's not a huge focus for me. The day after I make sure to drink my ERW (electrolysed reduced water) in the morning (check out my Ionfarms water ionizer add on ebay) which is hydrogen containing water. Broccoli extract is also a really solid liver enzyme/antioxidant booster

I think the body picks up on toxicity pretty well, I believe I would feel it if there was a lot of remaining toxicity going on. But at this point I am really satisfied with the results of these experiments. I am sure there are some other bases we should cover, secondary ethanol toxicity and things like that. I think I will do some more research on it eventually. But this feels good, that's for sure. Idk why people drink without vanillin, because it's way better hahah.

Blessings! - Nolan
 
I'm no expert but I wouldn't.

One of the most severe effects of serious withdrawal is seizure so......seems like a bad idea given the mechanism of action of alcohol on the CNS.
 
Light use of alcohol is generally ok for people with seizure disorders unless that disorder is being actively controlled by antiseizure medication (some of which interact with alcohol).
Why would a person with seizure dosorders not be actively controlled by antiseizure medication?
 
Some studies have shown that alcoholism, or chronic abuse of alcohol, is linked with the development of epilepsy in some people. Research indicates that adults with epilepsy may have one or two alcoholic drinks a day without worsening their seizures or causing changes in the blood levels of their seizure medications.

More information here :
 
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