Drinking is fun sometimes. And, unfortunately, drinking is unhealthy. There are a lot of strategies to reduce hangovers, negative side effects, and damage to our health that are underutilized.
This is a relatively shallow dive aiming for simple interventions that make the biggest difference. This isn’t medical advice, I’m not a doctor. Please comment if I make a mistake, I’d like to know.
TL;DR: This stack from Life Extension is solid. Take it with alcoholic drinks to minimize liver damage and oxidative stress damage. Or, consider taking glutathione before or after a heavy night of drinking. And don’t forget to hydrate with electrolytes.
Alcohol is broken down in the liver in two steps.
First, ethanol is broken down by alcohol dehydrogenase (ADH) into acetaldehyde. The first product, acetaldehyde, is more toxic than ethanol. It is a major cause of hangover. Buildups of it cause flushing, dizziness, nausea, and headaches. It might be responsible for the more unpleasant aspects of being drunk, such as the memory problems, sleepiness, and lack of coordination .
Next, acetaldehyde is broken down by aldehyde dehydrogenase (ALDH) into the harmless acetic acid (acetic acid is what makes vinegar vinegar). If there is a problem with ALDH via genetics, alcohol is substantially more toxic!
A fast ADH or a slow ALDH cause a buildup of acetaldehyde.
The overflow system, for when there is a lot of alcohol or an underperforming ALDH, is called the Microsomal Ethanol Oxidizing System (MEOS). MEOS does a lot of important metabolism already, and by having to process alcohol, it can’t do its normal functions, which can lead to a buildup of toxic byproducts.
Glutathione: Key Antioxidant
Glutathione is an important naturally occurring antioxididant, that is, it stops the harmful chemical stress caused by free radicals in the body. Glutathione is generated by the body and might be supplementable.
There’s a lot of debate about how effective it is to take glutathione orally . Due to how important glutathione is, it seems worth trying. A stack like this one by LifeExtension seems like it might work, and comes complete with a long list of citations.
Other supplements and foods
To indirectly increase glutathione levels, these might help:
- Food containing sulfur. Uncooked meat, garlic, eggs, nuts.
- Foods or supplements containing selenium. Brazil nuts, mushrooms, seafood.
- Vitamin C 
- Cysteine or N-acetyl cysteine (NAC)
- Vitamin E
- Milk Thistle Extract
- SAMe 
- r-Alpha Lipoic Acid
Mixing with other drugs
The short story is that breathing is good. Depressants that also lower heart rate and breath rate are dangerous, and there are a lot of drugs that do this.
For a short list, avoid alcohol and these things:
- Benzodiazapines. Benzos stay in the system for 24+ hours, so if you took one yesterday it still might not be safe to drink today. They synergize aggressively, causing dangerously low breath rate and heart rate. (Also blackouts and intense stupidity, just read /r/drugs for an hour)
- Opiates. Breathing is good for you and your brain
- Sleeping medicine like Ambien
- Be careful with alcohol and muscle relaxants. This can exacerbate the physical effects of alcohol leading to a potentially dangerous lack of coordination and balance
- Altitude. It’s not a drug, but it’s hard to get enough oxygen at altitude. Drinking when you’re already feeling altitude sickness will not only hit harder, but increase risk of hypoxia.
Certain antidepressants, like Buproprion / Wellbutrin, don’t mix well with alcohol. When on an MAOI antidepressant, especially avoid red wine. Red wine plus an MAOI causes a new and fun sort of toxicity known as “cheese headaches”, which are uncomfortable and cause high blood pressure.
This isn’t a complete list of what to be careful of. Talk to your doctor, and if you don’t do that, check the Drugs.com Interactions Checker for prescription drugs or Tripsit.me Interaction Chart for illicit drugs.
Phenibut (β-Phenyl-γ-aminobutyric acid) is an anti-anxiety drug used in Russia. It’s unregulated and relatively unknown in the US, and can be purchased online. It’s a GABA-B agonist, meaning that it will relax muscles, increase feelings of relaxations, and decrease anxiety.
Many people take alcohol in order to reduce social anxiety. Phenibut reduces anxiety without many of the negative effects of alcohol. If social anxiety is the primary reason for drinking, Phenibut is a great replacement (sometimes).
Phenibut and alcohol synergize aggressively. This means that you can easily harm yourself by drinking like normal while on phenibut. But this also means that you can take phenibut and drink much less alcohol than normally, while still getting as strong a buzz.
Keep in mind: Like alcohol, phenibut is addictive, but causes fewer health issue than alcohol does. The withdrawal is known to be terrible if you do get addicted, so be careful. A good rule of thumb is to take it once or twice a week, and no more. The larger the dose is, the
Demographics and Genetics
Many people have mutations in the genes for either ADH or ALDH. Sometimes this is apparent from symptoms, and if not, an analysis of 23andme data could find something.
Mutations in the genes for ADH mean the risk of cancer from drinking is much higher .
Mutations in the genes for ALDH are very common and make alcohol substantially less healthy.
From Wikipedia, emphasis my own:
About 50% of people of Northeast Asian descent have a dominant mutation in their acetaldehyde dehydrogenase gene, making this enzyme less effective. A similar mutation is found in about 5–10% of blond-haired blue-eyed people of Northern European descent. In these people, acetaldehyde accumulates after drinking alcohol, leading to symptoms of acetaldehyde poisoning, including the characteristic flushing of the skin and increased heart and respiration rates. Other symptoms can include severe abdominal and urinary tract cramping, hot and cold flashes, profuse sweating, and profound malaise. Individuals with deficient acetaldehyde dehydrogenase activity are far less likely to become alcoholics, but seem to be at a greater risk of liver damage, alcohol-induced asthma, and contracting cancers of the oro-pharynx and esophagus due to acetaldehyde overexposure.
If you experience those symptoms and have that genetic marker, be aware! You’re more likely to get diseases from drinking alcohol. This is balanced by the cursed gift that the ALDH mutation makes drinking less pleasant, so at least those with it are less likely to become heavy drinkers.
Females have less active ADH and lower H2O levels relative to body mass. This means the MEOS system is more often used in alcohol metabolism, which is less ideal in general.
The older you are, the more toxic alcohol is. One reason is that glutathione synthesis gets worse with age .
Harm Reduction for Severe Alcoholism
Well. Given that someone is an alcoholic, there are multiple interventions that can reduce cancer risk and liver damage and increase overall health.
Alcohol consumption interferes with ability to absorb nutrients, plus alcoholic drinks tend to have very few nutrients! This means that alcoholics are likely to be seriously malnourished in both macro and micro nutrients. 
First, start taking Vitamin C, B Vitamins, and either Vitamin A or beta-carotene. If you aren’t a heavy drinker, skip the Vitamin A, as large doses above what is normal can be toxic.
Then, start aggressively supplementing whey protein. Next, get a blood test to see what you’re most deficient in, and start working to reduce those deficiencies.
If you’re malnourished or on a low protein diet, ADH works less efficiently, meaning that blood alcohol levels stay higher for longer. Like those with genetic mutations on ADH, this will cause more disease in the long run.
Summary and Stack Suggestions
Convention wisdom for alcohol safety, like how to pace your drinking and keep hydrated, are no less important. Overall, the more unpleasant the hangover or alcohol experience is, the more likely it is to be toxic. Reducing hangover symptoms is caring about your health.
My stack, optimized for convenience and health, is:
- Life Extension Anti-Alcohol Complex. This has Vitamin C, E, Selenium, NAC, Glutathione, and a whole slew of other ingredients that have some evidence behind them. This is a one-stop pill. Take one pill with each drink, up to 5 pills. If you’re taking this, be careful taking other supplements that might contain some of the same ingredients.
- Replenish that glutathione and drink water with a PowerPak of Electrolytes (which contains Vitamin C, B Vitamins, and Selenium) the next morning.
- Phenolic compounds on ADH and ALDH
- Alcohol and acetaminophen: Additive or negatively synergistic?
- There are two forms of glutathione one can take: L-glutathione (also called reduced glutathione) vs s-acetyl l-glutathione. Which one is better?
- The MEOS system: how it works and what it depletes, and what the tradeoffs are
- Healthy balance between NADH and NAD+ levels. Impacted by alcohol?
- Relationships Between Nutrition, Alcohol Use, and Liver Disease. [link]
- Alcohol Metabolism: An Update. July 2007 from the National Institute of Health sub-department National Institute on Alcohol Abuse and Alcoholism [link]
- Glutathione Depletion and Recovery After Acute Ethanol Administration in the Aging Mouse. Vogt 2008. Biochem Pharmacol. [link]
- Bioavailability Study of an Innovative Orobuccal Formulation of Glutathione. Buonocore 2015. Oxiditative Medicine and Cellular Longevity. [link]
- Enhanced Glutathione Levels in Blood and Buccal Cells by Oral Glutathione Supplementation. Richie 2013. FASEB Journal. [link]
- Vitamin C augments lymphocyte glutathione in subjects with ascorbate deficiency. KJ 2003. Am J Clin Nutr. [link]
- Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol‐associated cancer in heavy drinkers. Homann 2005. International Journal of Cancer. [link]
- Overview: How Is Alcohol Metabolized by the Body? Zakhari. [link]