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The Highbrow Paleo Guide To Binge Drinking: Addendum, Further Discoveries, And Thanks (I wuv U guys)

30 Mar

It has been a while since I wrote the Highbrow Paleo Guide To Binge Drinking and there has been an outpouring of positive reactions from many readers. People say that they have eliminated hangovers, that they feel well after a night of drinking when they might have otherwise had a rough day, and that they generally don’t see side effects from drinking like they used to. Others have had less success and this calls for some trouble-shooting. There have been general questions about what is essential and what is icing on the coconut flour paleo cake. Which are the core aspects of that enormous list of supplements and foods and which are redundant in combination with other supplements or foods? I will clarify my thoughts on the matter. I will also address some scientific tidbits and share new discoveries. This post will tie up some loose ends and right the ship for smooth sailing.

The core of the regimen is a handful (not literally, phew) of supplements and supplement types along with some foods and practices. Pantethine is hugely important for reducing the acetaldehyde accumulation from ethanol metabolism, and everyone except for those who will get significant facial flushing when drinking will benefit from it in this way.

To answer WCC Paul’s question about the specifics of facial flushing in response to alcohol: some people have a polymorphism where they only have one normal copy of the ALDH2 gene which codes for the enzyme acetaldehyde dehydrogenase (see the original post for the diagram), which metabolizes acetaldehyde to a safer molecule. One common copy and one mutated copy results in significantly impaired acetaldehyde dehydrogenase activity, whereas two common copies means better acetaldehyde metabolism (1). Since coenzyme A which is produced from pantethine must activate this enzyme to exert its effects on metabolism, it is like putting gas in a broken-down car to supply more coenzyme A from pantethine. No go. Pantethine has many benefits besides the aforementioned so this doesn’t mean that those who flush shouldn’t think about it anyway. Byron Richards has written a superb article about some of the benefits of supplementing with pantethine including better lipid metabolism, brain health and a reduction of fat accumulation in the liver(2).

It is estimated that this extreme facial flushing is mostly a phenomenon occurring in The Orient, to the tune of 50% of the population in some places.  That is a significant percentage of the world. It is a smaller percentage of the readers of this blog but I suspect that we have enough East Asian readers to make this relevant. You will know who you are.

This is your face on acetaldehyde

Along with pantethine it is imperative that you maintain a nutritious diet and get extra Vitamin B1, Vitamin E, and Vitamin C on the day of drinking. These will protect the body from the stress of acetaldehyde. I favor getting these from food but an acute supplemental dosage if you haven’t been paying close attention to your diet will probably help.

Embarrassingly I unintentionally omitted Astaxanthin from the original article. Astaxanthin is a carotenoid and is responsible for the pinkness of salmon, shrimp and flamingos. It is one of my favorite antioxidants and definitely protects rodents from alcohol-induced liver injury (3). Its benefits for humans are quite impressive, and in placebo-controlled trials it can radically reduce oxidative stress and inflammation in most areas of the body(4). It appears to be an ideal nutrient for dealing with acetaldehyde toxicity and one that I recommend highly.

Flamingos know how to party

About using rat studies: I mentioned in the original post that it was useful to hazard a guess as to whether or not what protects rats can in similar ways protect humans, and I stand by it. This isn’t a precise protocol to begin with, it has to do with experimentation because all of us are in a different state with regards to our health. In assessing how we feel in our everyday lives and getting blood tests we can make adjustments as needed.

Rat studies aren’t a great reflection of what happens in humans all of the time, but when it comes to the ability of nutrients to protect an organism I think that the inference from rat to human is a lot more tenable than guessing what might kill a human because it kills a rat, as thousands upon thousands of studies on obese rats with metabolic syndrome spectrum diseases and disorders have suggested. Routinely rat studies are used by the unknowing to justify the notion that a particular food causes harm, when the conditions that the rats are living in are unnatural and don’t apply to healthy humans in the real world. Just adding additional basic nutrients to the diet and making rats exercise can alleviate many of the problems that a so-called “high fat”, “high sugar” or “alcoholic” diet and lifestyle can cause the little critters. It is for this reason that whenever I see rodents getting a disease from something or other I have to ask “what could we add to save these furry little guys?” and oftentimes there is much that can be done.

“Help me Astaxanthin, you’re my only hope!”

But it is often correct to extrapolate to humans as long as we employ comparative anatomy, knowledge of the mechanisms and of the different possible contexts. Like I just suggested with Astaxanthin, when the mechanisms are the same in both humans and rats and when all reason points us to a conclusion, we should act on it. I suspect that increasing glutathione and other protective molecules in the liver will protect humans as it does rats, this is my experience, this is the experience of others, and I think I’m justified in believing it.

That being said, humans have to live for a very long time and rat studies often take place over the course of months. So we can’t infer that these things don’t cause great harm to humans in the long term because they don’t cause rodents to become diseased in the short term. Chronic toxicity can be mitigated for a time in some cases but over the long-term it can add up to a significant negative effect on the body. This is where I realize the limits of such a protocol but I still think that there is much merit in looking at damage reduction on the occasions we might over-indulge.

Back to the implementation of the protocol. Anti-inflammatory nutrients may be frivolous in some cases. If we are eating and living in a generally anti-inflammatory way we will be greatly protected from excessive systemic inflammation by default. However they can be a great boon for some people who are still fighting inflammation, and the nutrients that I selected are like an insurance policy, they protect rats quite well and the same mechanisms can be demonstrated to work in humans.

Combinations of anti-inflammatory nutrients may be synergistic or redundant. If you take curcumin you may not need ginger but some supplement companies feel that their supplements should contain both. If you take quercetin, you might not need resveratrol. I suspect that you only need one strong selective inhibitor of the COX enzymes prior to drinking. One of the options that I suggested in the original post will probably suffice. Save your money and buy the cutie at the bar a drink instead! Most of our anti-inflammatory potential should come from staying healthy with a good diet and lifestyle anyway.

The guide is meant to be an adjunct to good health and good diet. The healthier we are when we drink, the less it will affect us negatively. It is not just that we have more life to destroy but that the toxic effects are actually lessened when we are in good health. Although I mentioned it in the disclaimer, it needs repeating. For those who are in the process of getting healthy but aren’t quite there yet, the effects of alcohol are more dire than  for the stunning examples of health that we see all around us in the health community. If you have intestinal dysbiosis, diabetes, are inflamed and have high levels of the most common clinical marker for chronic inflammation C-reactive protein (CRP, one of the most common markers for chronic inflammation) then alcohol is going to be more of a burden on your liver and body in general. The inability of the immune system to be controlled so that it heals and doesn’t hurt is vital to getting away with abusing one’s liver. A dysregulated immune response is what turns mild damage to hepatocytes into cirrhosis over the years. The level of CRP conducive to good health is generally recognized to be 1.0 mg/dl or lower. Many of us have a CRP level of 0.1 mg/dl and I doubt that anyone on the paleo diet or other healthy diets long term will have appreciable levels of chronic inflammation, but you should check to make sure.

You will want a liver enzymes test (measures liver health) and general metabolic panel if you are serious about boozing healthfully. It’s all up to the individual what they want to do, but I’m assuming  that we’re all interested in health. Subjective assessments of health upon waking up and drinking some water after a night of drinking are good measures of adaptability to alcohol, but you can never be too safe.

Now for some trouble-shooting and further answers to questions about how to implement the protocol effectively:

Exercise: You should exercise some time in the day before drinking. You don’t have to exercise during drinking. Running away from a police officer after urinating on his car DOES count over the course of the days that will follow, but I would discourage that. We are degenerates, not jerks.

Glutathione-supporting supplements:  Glutathione-generating nutrients are very useful but taking many of them might be redundant like with anti-inflammatory nutrients. Then again maybe not, I can’t give my definitive stance on that right now. N-acetylcysteine will directly generate it and is a top choice. Silymarin from milk thistle is a good choice for preserving glutathione status in the liver as well. Getting enough sulfur will allow you to synthesize more glutathione, and foods like whey, milk, and fruits and vegetables may be ideal for supplying or generating it (5). Green tea has also been shown to increase glutathione levels significantly(6). I can’t give any clear rules to follow here, but do look into ways to boost glutathione levels on a daily basis; it will help you greatly when you need it. Take the supplements days in advance of drinking. This is very important because we don’t want to  be glutathione-depleted when we are drinking and take a few pills on the same day, hoping to increase our antioxidant status all at once. Glutathione is like money in the biological bank, build it, maintain it, and spend it as you see fit, but don’t try to spend what you don’t have. It takes a while to build up to highly protective levels.

Milk thistle/silymarin: try it alone before trying it with alcohol or other supplements. It can produce what I assume to be a detox reaction in some people, and then they go and blame the protocol for not working, but they end up feeling better when omitting the milk thistle. If you get a good response or no response to milk thistle then take it two weeks at a time, two weeks off, as well as prior to drinking. I think that there is wisdom in rotating herbs, because they can potentially have adverse side effects if used for prolonged periods. I can’t say for sure if milk thistle has chronic toxicity but there are some reports of it eventually impairing the liver’s ability to function properly. However there is no reason to think that it is harmful when used in moderation and at opportune times,  indeed, the opposite is true.

New discoveries that weren’t included in the original article besides the ones already mentioned:

I mentioned in the original article that there were mechanisms by which alcohol harms the body other than  oxidative stress and acetaldehyde toxicity, but assumed that my protocol would cover the rest because rats are usually in good health after these interventions.  However alcohol can also lead to dysbiosis, an imbalance in populations of symbiotic and pernicious microorganisms in the gut. We disinfect wounds with it, marinade meat in it, and drinking it is like going nuclear on our gut flora. This isn’t necessarily a deal-breaker, because experiments show that the effect can be reversed with probiotics and prebiotics (7).  Some lactobacillus strains and some fermentable fiber. Yeah yeah I know, more stuff to add to the pile of pills and foods, but this issue strikes me as uniquely important. Hopefully most people are getting a moderate amount of vegetable and fruit fiber and eating some probiotic-containing foods anyway and the point is moot. The researchers used prebiotic oats that feed gut bacteria, and lactobacillus GG to counteract the leaky gut from intestinal dysbiosis. Mmm! I’ll just add that to my rice flour, whey protein, high oleic sunflower oil and pile of pills. Oh wait, that’s not a joke I actually eat those things. Stabby is inadvertently on the lab rat diet, hold the Crisco!

Rat gut flora is different than human gut flora but I think the same principle probably applies. Maintain certain levels of certain beneficial bacteria. Stomach cramps and excessive flatulence in response to fibrous foods are  good subjective asessments of the state of one’s gut flora.

There is a great deal of anecdotal evidence that a little bit of sodium bicarbonate (baking soda) helps to prevent a hangover. The mechanism is likely as Dr. Ray Peat suggests, carbon’s buffering of lactic acid buildup (8). Alcohol metabolism interferes with the breakdown of lactic acid, which can raise the pH of the cells and blood, causing inflammation and fibrosis as well as interfering with energy production. Having enough Co2 available to buffer it will help to offset this effect. It certainly helps athletes to perform better, however it might take a few weeks of taking it to see a benefit (9). Consider it! It can potentially impair the efficacy of stomach acid so be sure to take it during a non digestive period.

Finally, don’t forget to hydrate properly; not too much or too little. Alcohol is a fluid but also a diuretic and can be dehydrating. “Oh dear, did he just tell us to drink enough water?! What’s next, get to bed at a reasonable time? Duh!” While it may be obvious, it can be easy to forget. We may also benefit from electrolytes which are depleted by drinking. Coconut water or various electrolyte supplements will help us feel our best and rehydrate. Verily this is an extension and additional detail of the overarching theme we have been discussing: be well-nourished if you wish to drink in excess. One can find all sorts of essential and non-essential nutrients that can protect the body against alcohol and they are invaluable. Some more that I didn’t mention already are selenium and magnesium (10). Those are pretty basic to any healthy diet, but this further illustrates the benefit of being well nourished when drinking.

And there you have it. Another segment of The Highbrow Paleo Guide To Binge Drinking: complete! As always, share your stories, your personal favorite remedies,  and share this article! This has truly been a team effort; I write these articles but can’t take all of the credit.












The Highbrow Paleo Guide To Binge Drinking: Mitigating the deleterious effects of ethanol on health (or, How To Get Shitfaced With Impunity)

26 Dec

Part two can be found here (seriously consider reading it, the percentage of people who read the second one is low and it is important)

Disclaimer: If you are a recovering alcoholic/recovering from a health issue or are a modern puritan, this blog post may not be suitable for you. In the case of 1. Good luck. In the case of 2. Get ye gone! I’m sure even reading this blog is sinful in some way. Are you still here? Get! Shoo!

“Paleo diet? But I like booze!”

Is this you on New Year's Eve?

And I like it too. Hi I’m Stabby and I love the sauce, but I also like to be healthy. It is sometimes assumed that these things are mutually exclusive, and that anything more than an ever so modest consumption of alcohol is a deal-breaker when it comes to our health. The notion that excessive drinking is damaging to health permeates the culture, and unlike some common beliefs about health, there is much truth to it. The list of maladies caused by excessive alcohol consumption is quite long, and excessive drinking is no laughing matter. However, some of us have social lives that may occasionally lead us into situations of being passed out on a bathroom floor with clever sharpie artistry augmenting the beauty of our visages. Shit happens, and that is the point of this blog post. In this post I’m not encouraging binge-drinking, just suggesting ways of ameliorating the damage when shit happens. Hot tub parties happen, and judgmental parents in law happen. Some of us have a love affair with booze that isn’t going to go away, but it is my belief that as long as we exercise a little bit of restraint and take some precautionary measures we can have our booze and drink it, too.

But the thing is that various nutritional interventions, particularly nutritional supplements, have a licensing effect on people leading them to feel invulnerable to unhealthy practices like smoking, eating junk food, and drinking, and they take a healthy practice as a license to do more of those unhealthy things. It is a tempting response to the promises of damage reduction, but no matter what we do, we will never completely eliminate alcohol’s effects. “I’m 50% protected against the ill-effects of alcohol, so I can drink 50% more!” is bad reasoning, and it is easy to succumb to it. We want to make drinking less damaging, but we don’t want to use that as a reason to be reckless. Just because you have a helmet doesn’t mean you should run into a wall.

Whew, okay then. I really hate moralizing, so that’s the last of it you’ll hear from me!

Apparently this blog is called Highbrow Paleo, so I’m going to quickly address the Paleotude of alcohol. Our gut flora produce a small amount of ethanol, about 3g, every day. So it isn’t like ethanol is this completely foreign substance that we don’t know how to handle like synthetic trans fats; far from it. Drinking alcohol provides a lot more alcohol than we would have seen during the bulk of evolution, but if the metabolic pathways exist already then there isn’t as much reason to think that alcohol is something that we can’t metabolize. There is definite reason to think that it is problematic, but the degree to which it is depends upon the body’s response to it, and that’s what I intend to investigate in this post. Alcohol doesn’t belong in the same category as trans fats, and while it has been tied to many diseases it is my belief that a generally unhealthy lifestyle deficient in nourishment and high in unhealthy foods, combined with a lifestyle that is at odds with our biology, is the driving factor that determines alcohol’s toxicity. It is still toxic no matter what, but less toxic when we hack our biology with nutrition and other tools. This is a guide on how to do so.

Too much ethanol is toxic, but why? There are many reasons, but the main reason cited has to do with its metabolism inside the liver. Ethanol is metabolized to acetaldehyde, and then hopefully to acetate, because acetaldehyde  is very toxic; it is highly reactive and is the main reason why alcohol produces liver damage. When metabolism of acetaldehyde is sluggish, meaning that the aldehyde dehydrogenase enzyme is downregulated, it is a very slow conversion and we see acetaldehyde accumulate all over the place. In the liver of course, in the blood, the heart, and the brain. We all know that feeling and it isn’t a pleasant one. We want to reduce the amount of acetaldehyde that gets produced, and detoxify the acetaldahyde that does get produced while preventing the damage it does while it’s on the loose. Our bodies are well equipped to do this, but if they aren’t properly nourished or if the immune system is sloppy and sluggish, then repairs will turn into demolition and we won’t be built up again but torn down.

So we need to upregulate the aldahyde dehydrogenase enzyme first and foremost. This will clean up acetaldehyde and reduce the toxicity of alcohol by converting it into a more benign molecule. By far the most effective way I know how to do it is to take pantethine. Pantethine is the precursor of coenzyme A, which is needed for various metabolic conversions. One of them is the Acetaldehyde –> Acetate –> Acetyl CoA pathway, and its effects on reducing acetaldehyde in the blood are quite pronounced (1). Unfortunately, it is only effective in some people; for those who have significant facial flushing from alcohol consumption, pantethine won’t do much to reduce acetaldehyde after drinking. But for everyone else it is excellent for reducing the toxic acetaldehyde load. Those who get very flushy are out of luck here, and aren’t the best candidates to be drinking to the extreme in the first place, but then again there is much that can be done to make drinking healthier for these people, which takes us to the heart of the topic.

Even if we can find biohacks to reduce the amount of acetaldehyde we have to deal with, we can’t eliminate its production entirely, so we must protect against it and detoxify it. The best way to do this is by supporting the body’s natural defenses, the sulfur-containing antioxidant enzymes, namely glutathione, one of our best antioxidants and detoxifiers which works in tandem with the rest of our antioxidant team.

Much of the work in the field of alcohol research is done in rodents, because apparently it is unethical to try to kill people with booze. The evidence that can be garnered from rat studies isn’t a perfect reflection of what would happen in humans, but it can give us good grounds to experiment for ourselves, and usually the mechanisms are  the same in humans and rats and I’m confident that supporting the same defenses in humans will produce the same results in the major aspects discussed.

The format of these studies usually goes something like this: A big mean scary scientist guy tries to kill some rats with toxic doses of booze, oh sure it’s fun at first and every rat gets lucky, but sooner or later the alcohol takes its toll and the rats in the control group get diseases. The rats in the intervention group get the protective nutrients, and we compare the difference in health between them. Science, bitchez, it, like, works!

Significant improvements in health after alcohol feeding have been seen with basic combinations of nutrients that you can get at a supplement store. The scientists in reference (2) had this to say in their summary:

“Greatest protection against anesthesia and lethality was obtained at 2 mM/kg with each of the following:l-cysteine N-acetyl-l-cysteine, thiamin HCl, sodium metabisulfite, andl-cysteic acid. A combination of l-ascorbic acid with l-cysteine, and thiamin·HCl at reduced dose levels (2.0, 1.0 and 0.3 mM/kg, respectively) gave virtually complete protection.”

Lucky rats, take that Mr. Reaper! L-cystine and n-acetyl-l-cysteine are precursors to glutathione, and ascorbic acid (Vitamin C) is important for glutathione’s redox. Thiamin, vitamin B1, appears to be important in protecting against acetaldehyde toxicity, and is greatly reduced by consumption of large amounts of alcohol. Sulfur (MSM in supplement form) improves glutathione status as well, acting as a rate-limiting factor for its synthesis from amino acids. We want to be supporting the synthesis of glutathione and our other antioxidant enzymes daily with a healthy diet and reasonable supplementation. But if we’re drinking frequently,  supplementation is going to be a boon. Physical activity prior to drinking is also very protective as it increases production of antioxidant enzymes and protects against ethanol toxicity in the liver and the brain. (3) (4) (5)

The active component of milk thistle, silymarin, has a pronounced protective effect on the liver when it is under stress from alcohol. It too works to preserve the health of the liver and its antioxidant enzymes (6), so do consider it.

Alcohol is intimately tied to another aspect of the cirrhosis spectrum diseases called fatty liver disease. Some of you may have heard about non-alcoholic fatty liver disease, which some believe sugar to play a role in. It is by far the less fun fatty liver disease to give yourself. The gist of it is that fat accumulates in the liver (steatosis) where it impairs its functioning, the liver becomes inflamed (steatohepatitis) as all of the damage needs to be repaired, but the dysfunctional immune system ends up being the nail in the coffin of the liver. There is fibrosis, an abnormal growth of  fibrous connective tissue, and our liver becomes very insulin resistant, creating problems elsewhere.  If we’re going to be abusing our livers, we should at least be sure that our immune system is on our side and we are doing everything we can to control inflammation. We’re degenerates, not imbeciles, thank you very much!

Possibly the biggest part of that is avoiding excessive amounts of omega-6 fatty acids, particularly the ones that have been oxidized and come from seed oils. Mice fed a diet high in omega-6 fatty acids develop the final stage of non-alcoholic fatty liver disease (and were lucky to not get any alcohol or it would have been worse) but conversely, when they are fed coconut oil or other saturated fatty acids it is actually protective due to the generation of adiponectin, a protective hormone that prevents insulin resistance and is a powerful anti-inflammatory signaler (7) (8). Adiponectin is lower in people with a lot of visceral fat, people eating low fat diets, low fiber intake, low activity level,  excessive inflammation, and other generally unhealthy practices (9) (10). But I’m assuming  that you’re health-conscious, probably following the paleo diet, and don’t need to be told to do any of these things. Regardless, you absolutely can’t be low in choline or your liver won’t be able to metabolize fat (11), so eat your eggs or else! Keeping the liver in good shape allows it to deal with a toxic load when it happens.

The list of maladies associated with excessive consumption of alcohol also includes brain damage and damage to the mucosal barrier of the gut, leading to a permeable or “leaky” gut. Reducing and detoxifying acetaldahyde will play a big role in preventing this, but we also want to enhance cellular defenses as much as we can. We already touched on glutathione, and it has also been found that polyphenols in strawberries protect the mucosa through stimulating production of defenses (12), and zinc has also been shown to be protective (13) (14). Various amino acids like glycine and glutamine will help to repair the mucosa, as well as Vitamin A. Carnosine, found in red meat, is an excellent protector of the brain (15) As are all sorts of berries. These things are all prevalent in the paleo diet for most, but it may be wise to ensure an especially high intake around the time of drinking or afterwards. Bone broth and gelatin have significant amounts of glycine, glutamine, and arginine which protect the gut and liver from alcohol as well (16) (17). It would be a great next-morning breakfast along with coffee or tea.

There are many nutrients that can curtail the inflammatory cascade that occurs when the liver is damaged, and while the paleo diet is generally strongly anti-inflammatory, extra ammunition will help nearly anyone. Ginger tea, quercetin, curcumin, resveratrol, and various herbs and spices protect the liver against ethanol toxicity and are helpful prior to or after a night of drinking (10) (18) (19) (20) (21). Red wine and quercetin are apparently a match made in heaven as red wine facilitates the absorption of quercetin (22). Score one more for booze! How’s that for healthy pills in your drink? Bound to confuse somebody, but not you.

Of course we want to stress moderation if possible, but if you find yourself just a little too drunk, consuming sugar will eliminate the alcohol from your blood faster (23). I recommend fresh fruit, which also has other protective elements.


Prior to drinking

  • Exercise
  • Pantethine
  • Glutathione-supporting nutrients: n-acetyl cysteine 500mg, alpha-lipoic acid, 500mg, MSM powder or comparable amount of sulfur from food – 5g
  • Thiamin 100mg
  • Choline 500mg
  • Carnosine 500mg
  • Milk thistle 500mg
  • All kinds of spices
  • Berries
  • Gelatin
  • Vitamin E (gamma tocepherol and tocetrienols, not just alpha-tocepherol and definitely not the synthetic form)

During or just before drinking

  • Curcumin 500mg
  • Quercetin 500mg
  • Ginger tea
  • Resveratrol 200-500mg
  • Anything else that is anti-inflammatory
  • Vitamin C
  • Vitamin E

The next day

  • Tea including ginger tea
  • Coffee
  • Gelatin/bone broth
  • All other nutrients that were consumed prior to drinking, because they will be low

This isn’t an exhaustive presentation of ways to protect yourself from alcohol’s ill-effects, and everyone should search further to find more remedies that work. There are other mechanisms that I haven’t touched upon, but the tips and tricks proposed within this article are likely to be protective in other ways that weren’t mentioned. If you have a particularly good remedy please share it, and have a happy holiday season, hopefully you will remember it! Cheers.




























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