[Transcript] – How A Specially Engineered Bacterial Strain Can Allow You To Enjoy Drinking Alcohol Without Toxic Hangovers, With ZBiotics Zack Abbott.

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From podcast: https://bengreenfieldlife.com/podcast/zack-abbott-podcast/

[00:00:00] Introduction

[00:01:10] Guest Introduction

[00:06:04] Is alcohol going to kill you no matter what?

[00:12:46] What happens when you drink alcohol?

[00:20:18] The idea behind ZBiotics

[00:23:35] The safety issues of genetic engineering

[00:30:09] The lack of liver enzyme and the use of anti-histamines

[00:35:33] DNA in ZBiotics’ probiotic strain

[00:41:24] The bacteria gut is used to seeing, but it doesn’t see the gut

[00:47:30] How to take ZBiotics?

[00:51:49] Are some types of alcohol cleaner than others?

[00:54:41] Electrolytes and hydrogenated water

[00:59:39] Plans for new products

[01:04:02] Closing the Podcast

[01:05:07] End of Podcast

[01:05:29] Legal Disclaimer

Ben:  My name is Ben Greenfield. And, on this episode of the Ben Greenfield Life podcast.

Zack:  The issue here at least in part is that we know the gut is a major source of acetaldehyde and we know that the liver has a great solution for acetaldehyde, but at that point, it's maybe too late. And so, basically, the idea here is that we just took a safe edible probiotic bacteria you already likely eat every day, whether or not you take probiotics and it's ubiquitous in nature and in soil, and then we engineered it to express an enzyme very similar to the one your liver uses to convert the acetaldehyde to acetate the same way your liver does. And so, the idea is you eat this probiotic before you drink and then it's in your gut. And, as acetaldehyde is forming in the gut, the bacteria are in there to help your body kind of deal with that acetaldehyde before mixing away in the bloodstream.

Ben:  Fitness, nutrition, biohacking, longevity, life optimization, spirituality, and a whole lot more. Welcome to the Ben Greenfield Life show. Are you ready to hack your life? Let's do this.

Alright, folks. So, as many of you know, I've not completely sworn off alcohol. I'm not on that longevity-enhancing bandwagon that says no cocktails for the rest of your life. As a matter of fact, I'm not even really celebrating sober October at least not in a strict sense of the word. I like to have an organic glass of wine every now and again or I should say a glass of organic biodynamic wine if you want to be a true healthy biohacker. I love to have like bitters, like digestifs and aperitifs, a lot of these wildcrafted cocktails where I'll take Italian Ebo Libo or one of my latest infatuations is Croatian Pelinkovac liquor and add a little bit of lemon and apple cider vinegar and sparkling water and make myself a cocktail at home. However, I will not deny that even in small amounts, alcohol can get converted into some things that long-term might cause some issues in your tissue so to speak. And, even though I endorse responsible consumption of alcohol, I think it's helpful to have some things around that you can help to control the damage with.

And so, that's where the story of today's podcast begins because my guest, his name is Zach Abbott. He actually was working at a research lab and came up with this crazy idea of engineering probiotic strains to actually help you digest alcohol better. That's my bastardized explanation. I know Zach's going to take a deep dive into the science today, but he's with this company called ZBiotics. He'll be able to explain exactly what it is and what it has to do with your desire to drink alcohol, probably a good topic to be talking about during our approach to the holiday season. But anyways, Zach, welcome to the show, man.

Zack:  Awesome. Yeah, thanks for having me. Excited to chat with you today.

Ben:  Yeah, for sure. And, I forgot to tell people during the introduction but I'll put shownotes for everything we talk about if you're listening or watching, go to BenGreenfieldLife.com/ZPodcast or if I'm cool and European, I could say BenGreenfieldLife.com/ZPodcast.

And Zach, first of all, it is kind of interesting that your name starts with a Z and you're in charge of a company called ZBiotics. Is that personal? Do you actually name your company after yourself?

Zack:  Yeah. Unfortunately, it was meant to be a placeholder name.

Ben:  Really?

Zack:  Yeah, yeah. We were–

Ben:  By the way, maybe Z was like the alphabet letter soup for the specially engineered probiotic strain or something like that.

Zack:  Right. It was kind of one of these things where I literally came up with the name in five minutes when I was planning for a pitch competition. It was meant to be like a placeholder before I even started the company and I thought, “Ah, if it ever becomes something, we'll change the name.” And, it's just something, but then we did a bunch of naming exercises after we were looking to launch the first product and the name really worked. We owned it and people kind of see Z is like a sciencey letter. We were launching the world's first-ever genetically engineered probiotic of any kind to go to market. And so, it sort of felt like a nice unique name to be the flag bearer for genetically probiotics as a category sort like ZBiotic. So, forever it'll be–

Ben:  You're right. Yeah, z does sound scientific. It's kind of like NASA or the Russians, right? Anytime you drop something like that in a conversation about science, you become instantly credible. So, I think we could throw Z into that equation too.

Hey, million-dollar question though before we get into what an engineered probiotic even is or how this came to be. Do you actually drink? And, if so, just to break the ice here, what's your cocktail of choice or your drink of choice?

Zack:  Yeah, I do drink although definitely less since started running this company. And, in the amount of work I have, it's sort of like I find myself having less and less time for sort of social activities. But yeah, when I do drink, I say my favorite cocktail if I'm just relaxing is a Boulevardier. And then, I'd say my favorite cocktail if I'm out having fun and socializing with friends is probably whiskey soda.

Ben:  I have no clue what a Boulevardier is. Can you explain?

Zack:  It's a negroni but with whiskey instead of a gin.

Ben:  Oh, okay. So, the fast track for getting drunk is an Italian. I get it. I've had some experience with negronis.

Now, do you have any thoughts on this, I think probably Dr. Andrew Huberman, bless his heart, is largely responsible for this craze of people pretty much like swearing off alcohol completely? And, of course, there's a surge in these alcohol replacement drinks that technically aren't alcohol but mixed different herbs and things like that. What do you think of this whole shift towards people just saying, in general, alcohol is going to kill you no matter what?

Zack:  Yeah. I mean, I think that look, we know alcohol is not good for you. So, if that works for you, I think obviously it's great. That being said, I also think that for some people a sort of an all-or-nothing solution is not sustainable. And, that's okay too if you decide to drink alcohol just choosing sort of responsible choices and drinking moderation and anything you can do to basically kind of mitigate the damage that we know alcohol always does for us. So, look, if you're happy with full sobriety and don't feel that impacts your life, then I think that's great. But, a lot of people find that it's a normal and healthy part of adult social interaction and works as sort of a social lubricant, it's something that's enjoyable for the flavor and that kind of uniqueness of the beverages. So, I think that that's also okay. It's an important part of your psychological health in many cases when engaged in responsibly. And so, I think [00:07:36] _____.

Ben:  Yeah. You obviously know way more about the interaction of alcohol with human physiology than I do being steeped in the science of this, I suppose, and even developing probiotics help the body deal with this. But, what do you think about the notion of alcohol as a hormetic stressor? Meaning, small responsible amounts that don't get you inebriated that you use in the same way you might use a wide variety of plants and herbs and spices might have a little bit of a cellular resilience-inducing effect, just like this concept that things that could kill you in large doses like spending three hours in the sauna, or an hour in an ice bath, or eating a giant shopping cart full of kale might not be that great for you, having little bits of alcohol might actually induce some kind of a hormetic stress. 

And, the way I think about this, and I'm curious to hear your thoughts on this is that a lot of times when alcohol gets thrown under the bus, it's because people are using large doses of it and some of the studies don't really break out the difference between someone having let's say a small glass of wine with dinner each night and averaging based on that maybe seven drinks a week and someone who's having like seven drinks on a Saturday night and just flooding their body with those toxins.

Zack:  Totally, I couldn't agree more that sort of lumping the behavior of drinking into sort of one broad category is definitely massively oversimplifying how humans engage with alcohol. And interestingly, we see that some of the cultures that have the most longevity alcohol is an important part of their diet and in every single one of those cases that alcohol is used in moderation. And so, I think that it is a reasonable hypothesis. Obviously, that's correlative, so there's no real data to support that the alcohol itself is creating any form of longevity but it's a reasonable hypothesis and it's also reasonable to say that alcohol when engaged in responsibility is not necessarily going to be uniformly detrimental to longevity and kind of your overall health. 

And so, I think it's interesting idea. There's a lot more data that needs to be gathered here because of the fact that, like you said, it's a perfect example. Seven drinks over seven nights versus seven drinks all in one night will have a very different effect on your health even though both were the same amount of drinks in a week.

Ben:  Yeah. I'm glad you brought up that blue zones type of piece where you do look at a lot of these long livid hot spots. And, alcohol maybe the Seventh Day Adventist aside seems to be a little bit of a staple. I think it's kind of contextual though. It's like if you're having a glass of wine or an aperitif or a digestif while surrounded by a bunch of people laughing and breaking bread in a parasympathetic state and full of joy and social engagement, that's obviously different than drinking three beers on the couch by yourself after day of work while you watch Netflix to drink away a little bit of stress.

Zack:  Absolutely, 100%. And, I think that for me, that context is actually what the most important part about it. For many people, alcohol is a good kind of platform or behavior that goes along with a lot of healthy social interaction. And so, in some cases sort of an effort to go in these all-or-nothing sober October or dry January. It also becomes socially isolating sometimes because people like, “Well, I don't want to go out because I'm not drinking.” And, that correlation in and of itself is maybe not all the most ideal. But, I think that this concept of all or nothing puts people into situations where they're making kind of either/or decisions, which I think can be detrimental in its own way because psychological health is also very important.

Ben:  Yeah, yeah. You'd be surprised a number of people I've run into who have said, “Well, I'm still going to go out and tie one on socially,” but they're actually using psilocybin. I must have run into like four people in the past couple of months alone who are micro-dosing with psilocybin instead of drinking alcohol in the evening and just figuring out a different way to kind of spin the dials.

Zack:  Super interesting. I think that as we sort of culturally evolve and understand like the health effects of different sort of substances that we ingest, I think that we're going to find the ideal situation. And, as long as we're committed to improving our health both our biological health but then also our psychological health and social health, all these things together, I think we're going to find some really cool–I think, some cool practices are going to emerge. I think that's great.

Ben:  Yeah, done. This podcast is officially over. Drink responsibly with other people, not too much at a time, and use psilocybin occasionally. Alright, thanks for listening, everybody.

Zack:  Yeah, perfect.

Ben:  No, I'm just kidding.

So, the interesting thing is that I think a lot of people might not realize what exactly is going on when you metabolize alcohol because from what I understand, it's not exactly the ethanol that's the issue, it's the byproducts that's being broken down into. Can you explain exactly what's going on and why alcohol would be problematic as far as its potential as a toxin?

Zack:  Basically, at the highest level when you drink, you ingest the ethanol. And then, that goes into your stomach and your intestines and it's most of it is pretty rapidly absorbed into your bloodstream. The ethanol then circulates throughout your bloodstream and has the effects that it has and then it makes its way to the liver where it's [00:13:28] _____ from a detoxification standpoint, it's sort of broken down in two stages. So, the ethanol gets converted into acetaldehyde using one enzyme and then that acetaldehyde is subsequently broken down into acetate using a second enzyme. So, that acetate, essentially it's vinegar, it's innocuous if anything, it's a short-chain fatty acid. It can be beneficial. A lot of metabolic fates happen from acetate, but at that point, from a toxicity standpoint, your body has successfully detoxified the molecule. That intermediate acetaldehyde is highly toxic, much more toxic than ethanol itself. The good news is that your liver is very good at both of those reactions. And so, very little of the acetaldehyde that forms in the liver actually makes its way into your bloodstream. And, it's not really a source of acetaldehyde.

That being said, what happens in the gut is a little bit different. So, I said most of the alcohol absorb pretty quickly, that being said, some of the alcohol that makes its way into your gut is broken down directly in the gut in large part by your microbiome. So, the microbes that are living in your gut before it can be absorbed into the bloodstream. And so, this is not a very significant amount of alcohol from a sort of intoxication perspective, but it actually becomes really important in terms of human health and the way you feel the next day because this alcohol is converted into acetaldehyde but then not subsequently into acetate like it is in the liver. And so, even though it's a very small amount of alcohol it's being broken down in the gut, almost all of it is being converted into acetaldehyde and not acetate. And so, the gut ends up being the major source of acetaldehyde in the body and we see that in scientific literature, it's well-established that colonic acetaldehyde levels are five to 10 times higher than blood acetaldehyde levels at any given time after a night of heavy drinking. And, this acetaldehyde is highly soluble, it gets absorbed out of the gut into the bloodstream, it circulates throughout the body like wreaks havoc, acetaldehyde like combine to DNA and bind to proteins and really junk up the gears in your cells and causes cell death, which causes systemic inflammation. Acetaldehyde can bind to receptors in your brain which causes nausea and anxiety and all these different things. And then, that acetaldehyde makes its way to the liver and it's broken down very efficiently in the liver. But, at that point, it's kind of like too late.

And so, when you kind of wake up the next day and you feel miserable, acetaldehyde is a major core of that. It's not the whole story. There are other things that are happening. So, the ethanol itself can basically binds receptors in your brain, which is part of what causes the intoxication effects but it also affects the quality of your sleep and ethanol also affects a lot of your hormone balances. And so, it affects the way you feel hunger and satiation, it affects the way your body deals with glucose. So, the glucose-insulin response like all these things are affected. And so, next that you're kind of dealing with downstream effects of largely those two molecules–there's sort of like other very small things that happen that contribute a little bit, but the major story is those two molecules. And so, those are the key elements of what your body is dealing with.

Ben:  Those two molecules namely being acetate and acetaldehyde.

Zack:  Sorry, ethanol and acetaldehyde. Yeah, right. We're pretty happy once we get to acetate. Yeah.

Ben:  Okay. Is there a dose-dependent effect? Meaning, if you drink a certain amount, do you wind up kind of like overloading the liver with acetaldehyde or ethanol that gets converted into acetaldehyde, and then at that point it begins to accumulate in the gut? Or, is there always some accumulating in the gut, some accumulating in the liver and it's just the stuff in the gut that we want to worry about the most?

Zack:  Yeah. So, for most people, the reaction from acetaldehyde to acetate is as fast or faster than the reaction from ethanol to acetaldehyde. So, in the liver. And so, usually, you're not going to overwhelm the acetaldehyde. You can overwhelm the whole system by drinking a lot like your liver can't keep up and so you're exposed to alcohol for longer. But, in terms of gut acetaldehyde, that is very dose-dependent. So, the more alcohol you drink, the more acetaldehyde is going to form in your gut, the more of that's going to get out into your bloodstream and sort of wreak havoc before it makes its way to the liver. And, it's not even just the volume, it's also the volume per unit time. So, drinking three shots in succession is going to overwhelm your system much faster than drinking three glasses of wine over the course of three hours or something like that.

Ben:  Yeah, yeah, that makes sense. And obviously, we aren't even talking about other contaminants that you might find in your drink of choice. If you're having the $2 margarita special with the high fructose corn syrup or you're consuming something that has processed sugars, the espresso martini with that potent combination of caffeine and alcohol like there's a lot of other considerations besides the acetaldehyde. But, I guess I'm hypothesizing here that my healthy responsible listeners are already choosing high fructose corn syrup-free and non-preserved laden sources of alcohol, so now the main thing they need to worry about is just the acetaldehyde.

Zack:  Exactly. I mean, yeah, you evaluate those risks like you would any other time like independent of the alcohol, like the other things that are in there that you have to make your own kind of decision about what you want to deal with those. But yeah, definitely right, like high sugar, high fructose corn syrup. Caffeine is actually really interesting when mixed with alcohol. There's a good data to show that it reduces sort of your risk tolerance. Excuse me, your risk aversion, synergistically even more so than the alcohol itself. And so, people who drink caffeine and alcohol are more likely to make really bad decisions like drinking and driving or more likely to engage in risky behaviors that they wouldn't normally do. So, definitely strongly encourage people to really be considerate about whether or not they should be having caffeine with alcohol.

Ben:  That was the original impetus for, I think, some nightclubs, I believe it was in Europe, kind of outlawing that Red Bull vodka phenomenon not only for the reason you stated but from what I understand it increases risk for things like stroke, atrial fibrillation, et cetera, which is kind of funny because I know a lot of folks, not a lot of folks but a handful of folks who will nod their heads in agreement that, “Oh yeah, Red Bull vodka,” and then they'll sip their hifalutin refined espresso martini at a martini bar, and it's pretty much the same thing as caffeine and alcohol, right?

Zack:  Yeah, yeah, exactly.

Ben:  Yeah. Okay. So, when it comes to what we can do about this, particularly the acetaldehyde, do you have a unique approach? And, I'd love to hear a little bit more about the science of how you could do some micro adjustments to the microbiome and actually equip the gut to better be able to deal with acetaldehyde. So, obviously kind of like a loaded question based on your history with engineering probiotic strains. But, I'd love to hear you get into this. We got time.

Zack:  Totally. Yeah, yeah, absolutely. I mean, look, I'll start by saying kind of like the high level and then kind of dig in a little bit that, as I said, I mean the issue here at least in part is that we know the gut is a major source of acetaldehyde and we know that the liver has a great solution for acetaldehyde. But, at that point, it's maybe too late. And so, the idea that we could deal with acetaldehyde in the gut seemed like a pretty straightforward idea as a way to kind of deal with some of the effects that drinking could have on kind of your next morning. And so, in looking at that problem, so my Ph.D. is in microbiology, I study bacterial gene regulation, I know that there's a lot of bacteria living in your gut, there's a lot of bacteria that is in your food that passes through your gut and we take probiotics which are live edible bacteria. And so, this felt like a really great mechanism for delivering that function of the liver into the gut. So, bacteria perform say like 3,000 biological functions, and most of those functions are for the purpose of the bacteria. And so, then sometimes sort of tangentially some of those functions could be useful to people. And so, the idea that we could apply genetic engineering to ensure that one additional function was added to a bacteria that could create a known kind of function or benefit for us universally was kind of the idea behind ZBiotics generally that we could just basically take a probiotic that we know is capable of performing these biological functions in the body and ensure that it performs a function that we find useful.

And so, then kind of looking around for applications of that, the knowledge that acetaldehyde in the gut is important for the way you feel after drinking, then I thought this would be a great kind of application of the technology prove out the concept of genetically engineered probiotics in a way that people could understand and really feel for themselves. And so, that's where we started. And so, basically, the idea here is that we just took a safe edible probiotic bacteria you already likely eat every day, whether or not you take probiotics, it's ubiquitous in nature and the soil. And then, we engineered it to express an enzyme very similar to the one your liver uses to convert the acetaldehyde to acetate the same way your liver does. And so, the idea is you eat this probiotic before you drink and then it's in your gut. And, as acetaldehyde is forming in the gut, the bacteria are in there to help your body kind of deal with that acetaldehyde before it makes its way in the bloodstream. And so, that's really at the highest level of the approach we took.

Ben:  So, you're basically turning the gut into a giant liver?

Zack:  I mean, in a way, yeah, or like a liver outpost, maybe. Yeah.

Ben:  Well, talk about playing God, but obviously people, I think, all joking aside hear you say something like genetic engineering and their eyeballs pop out, especially people in the health sector because apparently anything genetically engineered could be very risk-prone not have a lot of long-term safety data behind it. So, how do you address this idea that people are avoiding genetically engineered foods yet you're hawking this genetically engineered probiotic that digest acetaldehyde for you? What do you say to people who are concerned about the safety issues here?

Zack:  Totally. And look, I appreciate very much the concern that exists around genetic engineering. I think what's the problem has been is that the technology has been conflated with some of its applications. So, what I mean by that is that a lot of people are scared about GMOs and upset about GMOs because of the way they've been used. 

So, there is a large debate in this country and rightfully so around like the safety of, for instance, Roundup Ready corn, this idea that we can add more pesticides to our fields if we have this corn that's resistant to the pesticide. And so, the fact that the strain of corn is genetically engineered is not inherently what makes the product unsafe. The fact that we are adding more pesticides to our field maybe is what the problem is or is the debate of the problem. It's like, is this Roundup unsafe for our health and for ecological health? I think there's very reasonable arguments on that.

And so, unfortunately, the technology that enabled that business practice has been conflated with the safety issue itself. But, the fact that we've genetically engineered it has no effect on its safety whatsoever, it's just a technology, it's a tool to make final products. And, the analogy often used for this is that there's also a hot debate in this country around guns and gun control. And, I think that regardless of what side of the aisle you are on that conversation, odds are good that you're not saying that we shouldn't use metallurgy, the technology used to make the gun, right? Because you recognize that metallurgy could also make a spoon, which is a very safe product. And so, it's really a technology that enables kind of products. And so, we should evaluate the safety of the product, not the technology used to make it. And, with genetic engineering, I think that–so, that's a tool that can be used to make all kinds of products safe or unsafe. And, I think that there's some sort of misconceptions around what genetic engineering is.

You sort of mentioned like kind of playing God. And, in reality, I mean, I think that gives scientists a little too much credit like we are doing–basically, what genetic engineering is is we now have an increased understanding, better understanding than we did 20, 30 years ago about how life already alters its own DNA. And now, because we understand that better, we can guide that process more directly and more efficiently. So, 200, 300 years ago, we were doing the same thing of trade transfer with plant crossbreeding. It's a natural process that plants do and they essentially mash all their DNA together and a bunch of traits cross over and then we selected a plant that has the traits that we want like a juicier fruit or a better color or whatever it might be. It's a very imprecise process. Plants are relatively new to the game of gene transfer. 

Bacteria are 2 to 3 billion years older than plants. So, bacteria are much better at kind of editing their own DNA, and we've come to understand how bacteria do that. And, they do it very effectively, very efficiently. And so, now that we understand that process, we can guide that process better in the lab. And so, right now what I do for genetic engineering is I literally just mix live bacteria with DNA and then the bacteria will take up that DNA all on its own using processes it's already evolved to do. It will then match that DNA to its own existing chromosome and swap that DNA in to its own chromosome. It does all that itself and it knows how to do all that. So, I'm not really doing a lot, I'm just sort of facilitating a natural activity, and that is genetic engineering. And, when I do that, that creates a GMO.

And so, the process does not make the bacteria unsafe in any way. Now, it's a question of what that DNA is and how that affects the bacteria whether or not it's going to be unsafe. And so, with our first product, we genetically engineered the bacteria to express an enzyme that is present in 70% of all life on the planet, including many of the bacteria that are already in your gut. Your liver cells make this enzyme and many of the bacteria that in a soil that the bacteria already naturally engages with have this enzyme. And so, all we're doing is making sure that you're getting enough of a very common enzyme at the right time and in the right place. But, nothing we'd introduced into this is unseen by the bacteria or by your gut or by the external environment. So obviously, the product we're creating is very safe because we're not introducing anything new, it's really about a matter of optimizing for a specific use case of human health that nature didn't have any incentive to optimize for before. 

Ben:  Yeah.

Zack:  And so, when you think about the end product, that's really kind of the question about whether our product is safe or unsafe.

Ben:  Okay. And, not to excessively stereotype here, but you hear about like the red-faced Asian businessman who literally is very red-faced after say quaffing a few beers. And, the reason that I understand that's the case is because they lack a certain enzyme. I believe it is something like a dehydrogenase enzyme or something like that that breaks down the alcohol. Is that the same enzyme that you're genetically engineering a probiotic strain to produce?

Zack:  Essentially, yeah. So, the enzyme that the liver uses to convert, it's called acetaldehyde dehydrogenase. So, it's basically the enzyme that the liver uses to convert the acetaldehyde into acetate is mutated in certain people. And, that mutation is most common in people with East Asian descent. And so, what happens there is that the alcohol you drink, that makes its way to the liver and is processed in the liver, the alcohol is processed into acetaldehyde, but then that second step from acetaldehyde to acetate is not very efficient. And so, you get this massive kind of dose of acetaldehyde. Acetaldehyde among many other effects, it has is also a vasodilator. And so, it causes the blood vessels to swell which creates more blood kind of rushing to the surface and skin. And so, that's why you get that flushing reaction, and that's due to a huge exposure to acetaldehyde, which also has kind of other undesirable effects beyond just the flushing. But, most people have a functional version of that enzyme, they don't have that flushing action unless they drink a lot of alcohol in which point the acetaldehyde is building up in their gut–

Ben:  Yeah. Everybody will get a little bit of a red face, it's just some people don't make as much of the dehydrogenate so it might set in earlier. I think I should name, by the way, that another issue that I'm aware of that can cause that red face is histamine sensitivities which you can genetically test. And, a lot of people nowadays, including me, I've started to do this, will take like a natural anti-histamine prior to alcohol consumption. If you have poor histamine pathways, there's a genetic testing company. I don't know if you've heard of it, Zach. It's called StrateGene and they test you for all these so-called dirty genes like your nitric oxide pathways, your glutathione pathways, et cetera. And, one of my pathways that's heavily dirtied is my histamine pathway. And, a lot of high histamine foods would include fermented foods, canned fish like sardines that's a biggie; alcohol, particular things like wine and beer or even kombucha would be pretty high up on the totem pole too when it comes to histamine-producing compounds. And so, I think an antihistamine seems like a pretty good solution as well. And, as a matter of fact, when I drink, I've been using–I have a whole stack, so I take a little bit of glutathione later on. I've been taking a shot of your ZBiotics prior, but then I also use a little bit of an antihistamine as well. It sounds like a desperate attempt to be able to get away with alcohol consumption, but I'm all about a little better living through science if you're going to have a couple glasses of wine.

Zack:  That's exactly right. You could call it desperation, I think it's like, look, we're leveraging the tools we know as we understand the biology better and better. What's interesting about anti-histamines is that most of them actually have a sort of, I don't know, I guess you call a side effect that they're vasoconstrictors. And so, that also sort of masks that symptom of the vasodilation of acetaldehyde. So, that's sort of another reason why sometimes people who do have a flushing reaction find that antihistamines can help. That being said, that's really a combating symptoms rather than you're still being exposed to acetaldehyde just it's not causing vasodilation now.

Ben:  Yeah, yeah. Considering another hack that people use is the activated charcoal carbon type of absorbent post-alcohol consumption. I think the main reason I'm not a huge fan of that solution and why I like using ZBiotics and throwing a little bit of glutathione and antihistamine into the mix too is the activated charcoal, basically absorb any other supplements you take including anything you might take to help you sleep better like your favorite sleep supplement. And then, it can also kind of make you constipated as well. So, even though I think it does a good job absorbing toxins, I mean when you're talking about just like allowing your body to produce the enzymes in the gut biome that digest the acetaldehyde anyways seems like a pretty good solution.

Zack:  Yeah. So, I mean, look, actually charcoal is a pretty interesting one because that's sort of a thought experiment that didn't work. So, when you go into the hospital with poisoning and often alcohol poisoning, they'll pump you full of activated charcoal, but it's like a kilogram. And so, the volume in those pills of activated charcoal is on paper and in practice is shown to not have the absorbing amount is way massively thousands of times too small.

Ben:  Oh, really? Huh, I didn't realize it was that much smaller than what they use in the hospital. Wow.

Zack:  Yeah. I mean, literally, I mean, those pills are, whatever, a few grams if we're talking a kilogram or 2. There are papers showing that activated charcoal has absolutely no effect. And so, it was sort one of these things where like somebody's like, “Oh, well, we use this in an extreme scenario, maybe it'll help kind of this other one.” I think many of things you mentioned I think do have good scientific hypothesis around them, but with activated charcoal, I think we can be pretty confident that–and, your point though, the problem is quantity. When you're trying to match–absorption is one molecule, one molecule. They interact on a one-to-one scale. That's the ratio, stoichiometry is very ineffective. So, you have to have this presence of it the whole time that all the acetaldehyde is being formed for the hours that you're drinking, you have to have this molecule also present in sufficient quantities to facilitate binding. And so, that's fundamentally why we went to a biological approach. 

So, rather than sort of having a one-to-one ratio and a chemical reaction, which we've shown throughout the 6,000 years of human history that people have been drinking that they haven't been able to find sort of a chemical in nature that can one-to-one deal with this problem is we went to an enzymatic approach. So, the idea that one enzyme of acetaldehyde dehydrogenase is a machine. It can continue to break down more and more acetaldehyde every molecule it engages with. So, it's a much more powerful solution like one can break down many. And then, if we put in a bacteria, which is an enzyme factory, we can make–I was going to say the number. I can't even say the number. Millions or billions of these machines of these enzymes that can all break down molecules of acetaldehyde. So, we get a massive sort of exponential extrapolation of kind of the effect of acetaldehyde breakdown when we go into biology instead of chemistry.

Ben:  Yeah, that's pretty cool. Now, you said that when you make the ZBiotics that you take a probiotic strain and then you mix it with DNA, where are you getting the DNA?

Zack:  Yeah. So, I mean, that's I think where the art meets the science. Essentially, we want to design a piece of DNA that will basically integrate leveraging the bacterial ability to kind of integrate the DNA into its genome. We can basically direct where that happens by the way we design the DNA. And so, in the last 10 to 15 years, we've gotten very good at sort of reading and writing DNA. And so, we can basically make short strings of DNA using chemistry so then we can design exactly where you want it to go in the genome, and we can make sure that that edit is extremely precise and we know exactly kind of what's happening as opposed to the plant crossbreeding where you're just sort of mashing together whole genomes and you don't really have any control where that happens.

So, right now, we literally, you can just order that DNA, that strip of DNA to be made and the design of it. And so, if it's not well-designed, it's not going to integrate. And so, there is the bacteria need the DNA to look very similar to their own DNA are also not going to integrate it. And so, we have to design DNA that is very similar to DNA they already have and then we include the trait we want in that strip in a part of that DNA and then the bacteria are able to kind of integrate that.

Ben:  How do you make DNA? Are you just stringing together the, A, the D and the T, different nucleic acids?

Zack:  Yeah. So luckily, I don't have to make the DNA. There are many companies that are very good at synthesizing DNA. But yeah, I mean, fundamentally, it's like writing. They're just sticking the nucleic acids together in an appropriate sequence. And so, we've gotten very good at doing that very efficient. We, I mean, sort of like the synthetic biology community not we as in ZBiotics. I've gotten very good at synthesizing DNA pretty efficiently so that we can sort of do these projects.

Ben:  Yeah. How do you know it's safe though? I mean, how do you know I'm not going to grow a third arm in my gut from consuming something that's been genetically engineered?

Zack:  Yeah. I mean, I think that first and foremost there's no reasonable expectation that that would be the case. The fact that the string of letters of DNA is that's the instructional code for the bacterial cell. And so, whether the code itself, that's not going to have any effect on you as a human, it's just DNA. You eat all kinds of DNA and all kinds of different confirmations all the time. 

Ben:  If you eat meat, you're eating DNA, right?

Zack:  Absolutely. Anything you basically, yeah, that comes from a living cell. You eat meat, you eat plants, you eat mushrooms, any of that. It's all DNA and all of the code that we're talking about is in those cells that you're eating. And so, it's really just us putting them into different cells. And so, the question about safety would be not in the actual act of genetic engineering, it's in like what is the outcome, what does that cell look like at the end? What does it do? And, is that unsafe in some way? And so, basically what functions are you affecting? And so, the two ways to ask that question or the two kind of major considerations I think is like first and foremost, is the literal function you're putting in unsafe? So, in this case like the fact that we're programming the cell now to break down acetaldehyde, is that in some way unsafe? And then, the second sort of like kind of more broad question is the fact that the bacteria is now able to perform that function. Does that affect something else in its genome that would then make it unsafe? And so, those are kind of the two questions you have to ask. Again, like the tool made the product. Now, we have to ask, is that product safe or unsafe?

Ben:  Right.

Zack:  It can't mutate you. That's not how this works. That's not how genetics works. And, the fact that we've mutated it in some way does not mean that now it can mutate you. So, it's really about what function does it perform. And so, there's many things we do to test for safety in terms of like, is this product not safe? Is the function that's performing unsafe? Or, is it affecting some other function that would make it unsafe? And so, at that point, now, we're like, it's the same as if we find a new strain of bacteria in the wild and we want to give that as a probiotic or if we sort of crossbreed and make a new fruit. We want to make sure that did we–again, that's just another way of changing its DNA in some way. And, we've been doing that for hundreds of years intentionally and thousands of years unintentionally. And so, at that point where we evaluate the safety of the product the same everywhere. We look at toxicity, we look at allergenicity, pathogenicity. We look at all those things that are the standard battery of tests. We do them to an extreme level. We address the genetic engineering and make sure that we're not disrupting something in a way that could create a problem.

So, for instance, some techniques for genetic engineering involved using antibiotic resistance cassettes or mobile genetic elements, so pieces of DNA that are intended to kind of move around. And so, we make sure that we don't use any of those of things that could cause ecological problems. So, we don't use antibiotic resistance cassettes, we don't use mobile genetic elements in the final product or anything like that. So, all those things are just best practices that eliminate the risks that are innate or inherent to genetic engineering. And so, then what we end with is something that we know looks like anything else we would test. And then, we do all the standard safety testing that we do for any other kind of standard food.

Ben:  Okay, that's good that you do safety testing although you did just shatter my pipe dreams of becoming some kind of mutated ZBiotic superhero and getting some Spidey sense after–

Zack:  Yeah, we can game plan how to do that later [00:41:22] _____.

Ben:  Your secret Batman labs.

Hey, so you talked about antibiotics briefly there. And, it is interesting because I was looking into akkermansia bacterial strain recently and interviewed Colleen Cutcliffe from Pendulum and they've created a process in their lab that's basically just like an oxygen-free series of tubes like the human gut to make an akkermansia strain that helps to control blood sugar and digestion of fibers. There's another product I'm aware of. I forget the name of it, but like akkermansia you got to load with it for a few weeks to really start to see the beneficial effects. It's a lactate-digesting enzyme that you take multiple rounds of over the course of a week to gradually load your gut up with what it needs to digest lactose, the sugar and dairy. Now, with your product with ZBiotics, do you need to kind of load with it for a certain period of time and use it consistently? That's kind of part one of this two-parter. And, the second is if you were kind of doing that and you got in an antibiotic's regimen, would it kind of wipe everything out and you got to start from scratch?

Zack: Yeah. So, you mentioned akkermansia, it's a really interesting probiotic. The way that it functions or the way that it is required to function is it basically has to take up resonance in your gut. And, that can be really difficult because everybody's microbiome is different. So, your microbiome and mine are totally different and your microbiome today and your microbiome in three months will be very different. And so, the idea that something can get into kind of regardless of the different communities we all have in our gut, the idea that a single micro can kind of get in there and have a beneficial effect is really difficult to do. And, for the most part, this is why there is no FDA-approved drug that's probiotic-based at the moment because that consistency is incredibly hard to get. And so, like you say, loading up your gut for a week or months on in is kind of your best hope. And, with a strain like akkermansia, the good news is that many people's microbiomes already have it. And so, there is kind of space or a niche for that to hopefully seed your gut. t's not going to happen for everybody but it's a much higher probability than say lactobacillus, which is by the way the most one of the most common probiotics.

Most adults do not have lactobacillus in their gut or at least not in significant numbers. And really, the reason why it's probiotic is because it's a leftover of the dairy industry not because it's good for human health. And so, the idea that it could have kind of a benefit is pretty weak hypothesis. Akkermansia has a stronger one. It's more present, more common. But, generally speaking, this is a huge problem. It's a big challenge. As a microbiologist, I was well aware of this when we started ZBiotics. And so, I decided I wanted to design something that could sort of sidestep that complexity that we weren't worried about what was happening in our microbiome since it was such a huge and complex problem. And so, instead, I chose a bacteria called Bacillus subtilis, which is something that you likely eat every day of your life. It's ubiquitous in nature. It's on the surface of fresh fruits and vegetables. It's on the surface of your countertops, all these things. And so, it goes in your body all the time, and its natural life cycle is to pass through your gut. So, even though you eat it every day if you were to sequence your microbiome, you would find very little or no B. subtilis in it as a permanent resident, a transient member.

And so, by that mechanism, it passes through everybody's gut kind of the same. So, we don't actually have to see the gut. And, I actually think that's a good thing because your microbiome and my microbiome are very different. They may both be very healthy. And so, the idea of kind of trying to muscle something in there could disrupt the balance that your microbiome, the ecosystem that your microbiome already has, and that homeostasis. And so, we pick something that your gut is very used to seeing that does not see the gut. And so, for that perspective, we don't have to load up your gut to take advantage basically the idea that as this bacteria is kind of floating down the river, it's expressing this enzyme and the enzyme is what useful to you, not kind of the other things that the bacteria is doing. And then, you pass it out the other side and the function is no longer there. And so, then if you drink again, you have to take the product again because we don't want to see the gut. And so, then, therefore, the idea of an antibiotic disrupting it is not really an issue because it's not taking up residence in the gut. Yeah.

Ben:  Yeah. There you go. Take your amoxicillin like candy, folks. You're not going to do any harm, maybe.

Zack:  Don't do that.

Ben:   So, Bacillus subtilis that you called it, you couldn't just consume the fruits and vegetables and compounds that contain it and then it would produce the acetaldehyde dehydrogenase, you'd still have to have a strain that had been modified in the way that you guys modify it in your labs.

Zack:  Right, exactly. Bacillus subtilis doesn't naturally express this enzyme. Different strains potentially might, but they definitely don't. So, our engineering was large so the platform we built was about getting a lot of enzyme expression in the conditions of the gut. So, bacteria turn on and on, this is why I study in my PhD was how bacteria turn on and off different genes in different conditions. So, if a bacteria finds itself in a place where there's lots of nutrients, it will turn on metabolism and growth genes and it'll turn off some of its other important functions that it doesn't need in that moment. But then, if it gets stressed out or attacked by another bacteria, it'll turn off its metabolism genes and turn on like fight or flight mechanisms. 

And so, it's really, really amazing, bacteria are incredible biosensors and they can kind of react to very fine differences in their environment. And so, what we had to do was engineer bacteria that when it's in the gut would make a lot of the protein that we wanted and not turn that off in favor of something else. And so, we engineered this strain of bacteria to make sure that it was making a lot of that acetaldehyde dehydrogenase enzyme as it went through your gut so that you have that enzyme when you need it. Many of the bacteria in your gut are capable and do make this acetaldehyde dehydrogenase enzyme. It's just they're not making it necessarily at the right time and in the right amount. And so, you don't necessarily get the benefit of that enzyme. And so, we're just making sure you're getting enough of that enzyme at the right time.

Ben:  Yeah. You wouldn't believe the times the past couple of months that I've been to a party or a social event and handed out a few bottles of these and my friends have texted me the next morning and been like, “Dude, where do I get that stuff? I feel great this morning” It was the same friends who are drinking frankly a lot more than I do. And, I've always told them, take a shot of this. It's a little liquid shot, the ZBiotic stuff, for those of you listening who haven't seen it yet. And, I tell them to drink it because I think this what the label said right before you start drinking. But, what if you forget, could you still drink it after and it would work?

Zack:  So, it helps best before. And so, it depends on what you mean by kind of after, right? So, if you drink two drinks and you're like, “You know what, I should drink my ZBiotics. This might not might be a little bit more. And, you drink a ZBiotics and you have two or three more drinks, it'll help most with those two or three more drinks you have after. If you drink four or five drinks, let's say, and then you go home and you take it before bed, I mean at that point, a lot of the acetaldehyde that formed in the gut is probably already been absorbed in the bloodstream.

Ben:  Yeah, good point.

Zack:  And so, if you take our probiotic and it gets in there, it can help with what's left in the gut. But, anything that's out in the bloodstream, I mean some of that will cycle back into the gut and will have a second pass at it. So, it'll help, it's just you're not getting the full benefit of the product at that point.

Ben:  Yeah. Okay, that makes sense. So, like I mentioned, I'll use glutathione sometimes because I like that for helping the liver detoxification pathways.

Zack:  Exactly.

Ben:  And so, do you stack the ZBiotics in your own personal protocol or just in terms of alcohol management as a whole? Is there anything besides this myopic focus on alcohol dehydrogenase that you implement when drinking or that you recommend?

Zack:  Totally. I think that it's really important that we do not claim nor should anybody claim that they have this magical kind of cure-all get-out-jail free card that stacking a lot of responsible habits and behaviors together–

Ben:  Yeah. Well, that's why you're not a billionaire yet, Zach. Sorry.

Zack:  Right, exactly. So, the deal is that what you're dealing with your drink, there's a lot of things happening in your body, there's a lot of biology happening there. And so, there are different things that you need to address. And so, to your point, glutathione is a great way to kind of reload the cofactors of the enzymes that are functioning in your liver and systemically and in your gut. And so, there is some good data as a reasonable hypothesis behind that. I think that for me, the biggest problems are really sleep and this gut drive acetaldehyde as I've discovered for myself. So, ZBiotics and then I make sure that I'm pacing myself and I stop drinking earlier so that I'm not dealing with the alcohol disruption in my sleep. Ideally like to go to bed sober or close to it so that basically most of the alcohols effect on sort of the sleep wake cycle as I'm trying to sleep is mitigated so that I can get better sleep. And, I think those two things for me–

Ben:  That's a good point because you get that surge in gamma-aminobutyric acid, the GABA inhibitory neurotransmitter from the alcohol, then it just kind of wears off. Same thing if you eat a real high carb meal before bed, you'll go hyperglycemic. And then, as soon as your blood sugar drops sometime between midnight and 2:00 a.m. usually, you wake up with a cortisol release to mobilize more glucose. And, similar with GABA, once it wears off, you get a great two or three hours of sleep. Anybody who drinks kind of knows this, then you wake up at 1:00 and the rest of the night of sleep is pretty crappy although you can hack that by just having some sort of GABA precursor next to your bedside and dosing up with that. But, you're right, stopping the alcohol consumption several hours prior to bed really helps out with that GABA rebound.

Zack:  That's exactly right. Yeah. Basically, yeah, you're dealing with this big pendulum swing and while you sleep, which is pulling you out of your sleep cycle then dropping you back in it. And so, you really get crappy sleep when you kind of let that kind of chaos ensue while you're asleep. So, the earlier you can work through that the better, and the more you sort of pace yourself, the less loaded up that pendulum is, the smaller the swings are. So, I think that those are sort of important behaviors that I kind of include alongside ZBiotics.

Ben:  Yeah. You think there's anything to this idea that certain forms of alcohol are cleaner than others like high fructose corn syrup and fillers and preservatives aside like a lot of people say Mezcal, for example, is very clean. I know a lot of people in the Paleo and health sectors who swear by the Mezcal tequila, other people or the Mezcal tequila, some people say vodka and gin are more clean. Obviously, organic biodynamic wine seems to be pretty favored due to the lack of sulfites and preservatives. But, do you think there's anything to this idea of certain forms of alcohol being clean or does that affect your choices at all?

Zack:  I think that at that point you're getting into kind of incremental differences that may or may not have an impact depending on your own personal biology. So, I think cleanliness when we think about different kinds of alcohol might be the fact that basically in the fermentation process that makes the alcohol and then in the distillation process that makes the liquor, there are byproducts. So, in particular, the fermentation that can affect the flavor. And often, you really pleasing way. So, for instance, one of the byproducts of fermentation of wine, that's really common is actually acetaldehyde itself. And so, in addition to the acetaldehyde, you're creating sort of the metabolic processes of the alcohol. 

So, red wine has a really high amount of acetaldehyde like in the cup itself. And so, that has a sweet, it has a nice aroma, it sort of creates sort of a sweet flavor. And, there are other sort of aromatics that are byproducts that basically that the bacteria or the yeast make as part of the fermentation process which affect the flavor in ways that we enjoy a lot of times. And, sometimes they affect the flavor, whereas we don't, and this is what the art of brewing and fermentation are. And so, your body might have a reaction to a certain congener that somebody else doesn't have. It's the same as like hay fever or another allergy or something. You mentioned sulfites and these are things that some people might react to and some people don't. So, I think that the cleanliness of the alcohol, in general, it's an oversimplification but in general clear or light-colored alcohols have less congeners than darker colored alcohol.

Ben:  Okay, okay. That's probably the logic behind the gin, tequila, vodka-type argument.

Zack:  Exactly.

Ben:  Yeah.

Zack:  Yeah. And, brandy we know has a ton of congeners. And so, there is some, but generally speaking the correlation between that and the severity of the way you feel the next day are–there's not good data to support that that actually has a huge impact. And so, I think that for the most part with anything, this is very personal. So, if you notice that something has sort of an outside negative effect for you, that's probably because how that alcohol interacts with your individual biology more than kind of being a general rule of thumb.

Ben:  Yeah, that makes sense. Man, I got to stock up on more ZBiotics for the holiday drinking season here. Again, not that I endorse irresponsible drinking but I think it's a good idea to have a few bottles of this around.

By the way, I should mention when we were talking about solutions, I forgot two things. I'm super strict about minerals/electrolytes/hydration before and leading up to drinking just because of the increased urination that occurs from the diuretic effect of alcohol. So, that's one. And then, the other one I like is when I'm drinking water, if I'm drinking or I'm going to drink, I like hydrogen tablets. It's kind of this selective antioxidant. That one kind of flies under the radar. I don't know if you've messed around with that at all, Zach, but I've done a few very interesting podcasts on hydrogen that you can dissolve in water and it seems to have a really great anti-inflammatory effect that makes alcohol feel a little bit better, especially the day after.

Zack:  Yeah, that's interesting. I think it's an interesting hypothesis because we know that first and foremost, reactive oxygen species and oxidative stress is a huge part of what you're dealing with as your body responds to sort of systemic inflammation from the alcohol. So, something that's an antioxidant definitely could reasonably be beneficial. And, we also know that hydrogen gas in large part produced by the microbiome is one of the major ways that your body generally deals with oxidative stress. So, I haven't looked into the science specifically the hydrogen tablet and whether or not that's delivering a physiologically relevant amount or anything that, but I think that it's a reasonable hypothesis to be interesting to see.

In terms of electrolytes and hydration, I will say that, I'd love to address this a little bit, the science on that is really, really interesting. So, it turns out that even though we know that alcohol definitely does bind to and affect and inhibit the antidiuretic hormone which causes you to notice that you pee a lot, it turns out that actually most of the increased urination is just due to the fact that you are increasing your fluid intake. So, drinking three kind of beers would be or if you drink three glasses of water in quick succession, you probably also pee a lot as well. So, there's a lot of data out there to show that you actually at most really only pee one extra time. We see this additional urine flow right as your blood alcohol initially spikes, but then it normalizes relative to somebody who's drinking the same amount of another fluid. And so, the biochemical markers of dehydration like vasopressin and things that we normally see with other things that cause dehydration are not actually present when we drink and the next day in high numbers, which is really, really interesting. And so, that's not to say that electrolytes and hydration aren't a good idea, your liver and your kidneys are working overtime to deal with this toxin that you're putting into your body. And so, keeping your blood volume high with fluids is valuable, but it's sort of a nuanced kind of point here but you're actually not combating dehydration at all. And, I think that we all probably know that at the deepest level that things that make you dehydrated don't feel how alcohol makes you feel.

Ben:  Yeah.

Zack:  And also, if you kind of wake up feeling not great the next day, typically the thing that would normally make you feel better, which is a glass of water or two, doesn't really seem to help with kind of that next day misery. So, while I definitely would advocate for hydration and stuff, I just want kind of make that it's kind of one of these misconceptions around dehydration.

Ben:  I'm glad you brought that up. And, by the way, unless you're one of those people who's vaping or using nicotine products while you drink which makes you pee like a racehorse, but it I think about that study I think it was in the Journal of Strength Conditioning Research seven or eight years ago that compared beer consumption post-exercise with Gatorade, and I think they were looking at urine specific gravity and hydration markers and they found that beer essentially hydrated you to the same extent as Gatorade with a similar post-exercise recovery boost. Again, proceed at your own risk and I don't necessarily endorse beer post-exercise, but it is interesting. You're right, I had forgotten about that study.

Zack:  Yeah, yeah. And, there's been several. I mean, there are studies dating back all the way to 1942 that basically show relative urine. But, a lot of studies in rugby players in the '70s who are drinking alcohol after sport and stuff like that, and exactly there's a lot of really interesting studies about alcohol inhibiting creatine cycling and testosterone and things like that. So, recovery from exercise after alcohol recovery inhibits kind of recovery, but the dehydration element of it is sort of been because–it was basically the observation that we know that alcohol inhibits the anti-diuretic hormone, and we also just observationally notice that we pee a lot when we drink. It led to this hypothesis that became sort of fact in a lot of people's brain that alcohol causes dehydration, but interestingly it doesn't. You're basically more than compensating for the inhibitory effects with the amount. Beer is 95% water with the amount of fluid that you're already drinking.

Ben:  Yeah. Shattering so many myths.

Hey, so now that you have this secret Batman lab where you can take probiotic strains and genetically engineer them with DNA, do you think you'll ever make anything else besides just equipping people to drink more responsibly?

Zack:  Yes, definitely. By the way, I'm glad you threw that first product that way. The goal here is not, and you mentioned earlier, the goal is not around irresponsible drinking at all, the goal is much more around the idea that drinking is a normal part of our social interactions, it should not, hopefully, have an effect on sort of the next day, like all of your healthy habits and routines that you've been building and you're working so hard for the next day. So, the idea that if you go out and enjoy a holiday party or a happy hour with your friends that you still make your morning workout the next day, or you still kind of stick to your healthy habits and routines the next day. And so, it's very much plugging into other responsible behaviors you're doing around drinking. And, that's really what this product is intended for.

And so, with that in mind right, the goal of the company as a whole was never to kind of solve everybody's kind of next day and misery after drinking. That ended up being a really cool kind of first application of a technology that I'm really excited about, which is the idea that we can genetically engineer probiotics to do very specific useful beneficial things. right now, we sort of just take bacteria that, for the most part, are leftovers of the food and dairy industry. We mine them out of the ground and we say like, “Hey, eat this bacteria and I hope that one of these sweet thousand functions that it performs is going to be useful to you in some way.” And so, your microbiome is different than mine and so maybe it will, maybe it won't. And, the idea that we can take that and we can actually engineer it to overlay a function that we know is valuable. This to me seems obvious in sort of the next generation of probiotic that is really very specific and tailored to people's needs. And, I'm really excited about that. 

And so, when I was looking for applications at the tech, I noticed early on when I pitched some things that I thought were interesting kind of got a lot of glazed-over eyes. They were sort of scientific. But then, when I sort of pitched something that people really understood sort of the next day effects of drinking and it sort of this unresolved problem and there was very nice [01:01:45] _____ of efficacy so people could try it and feel the benefit. That was why it made sense. It's kind of an introduction to the world of this technology.

So, when we launched our first product in 2019, it was the world's first-ever genetically engineered probiotic of any kind to go to market. And so, we really wanted to do right by that technology and make sure that people were really excited about it and believed in it and could really feel the benefit of it. But ultimately, we believe that there are hundreds or thousands of different things that you can do with this to improve somebody's day and improve somebody's life. And so, we are building all kinds of products to do all sort of things. So genetically engineered bacteria to perform functions that kind of help with every aspect of your day from if it's getting better nutrition from the food you're eating, if it's dealing with some of the unavoidable sort of toxic elements that are in our water, in the air or in processed food that things that are just impossible to avoid in modern society or the things that can maybe help you recover better from very normal healthy responsible behavior. So, exercise is great but obviously, it causes an inflammatory response which can delay kind of benefits or kind of knock you off your routines. Occasional poor sleep and sort of that inhibiting your ability to function if we can help with kind of dealing with that. So, there are so many things that biologically or biochemically can happen in your body that a bacteria already is part of. And so, we can kind of interrupt or intervene in a lot of these kind of biological process to make products for sleep and mood and function and nutrition and all kinds of stuff.

Ben:  You got to do one that'll make dipeptidyl peptidase to help people break down gluten and call it GBiotics. Actually, no, call it BBiotics. Name it after me like you named yours after you. Called BBiotics for helping you fare at an Italian restaurant much better.

Zack:  Yeah. Our goal is, I think, that we can make products that basically help people deal with a modern life and hopefully that people, they kind of could pick and choose what's going to help with the kind of things we're dealing with. So, [01:03:56] ______ restaurants on the menu for you, and maybe we can make one for that.

Ben:  My special request, my feature request. Hey, this is all fascinating. For people who want to try this stuff out, I know we've got some discount codes and things like that for ZBiotics, ZBiotics I should say, if you go to the shownotes at BenGreenfieldLife.com/ZPodcast, that's right, BenGreenfieldLife.com/ZPodcast, ZPodcast, I will link to ZBiotics, I'll include a special discount code for you guys, links to other articles and podcasts I've done about alcohol and drinking and making your cocktails and ketone cocktail alternatives and all sorts of stuff. So, I'll make the shownotes nice and juicy for you, again, at BenGreenfieldLife.com/ZPodcast.

Zack, thanks so much for coming on the show, man. This is just fascinating. I love this stuff.

Zack:  Oh, thank you for having me. It was a blast to talk about this and I appreciate having a really cool science conversation.

Ben:  Alright, folks. I'm Ben Greenfield, Zack Abbott from ZBiotics signing out. Shownotes are at BenGreenfieldLife.com/ZPodcast. Thanks for listening.

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Imagine waking up to a morning with clear thoughts and a body that's ready to leap out of bed – even after a night that included a few glasses of your favorite Cabernet.

Sound impossible? Not anymore.

My curiosity always gets the best of me, especially when it involves the cutting edge of health technology. That's why when I heard about today's guest Zack Abbott‘s quest to conquer the after-effects of alcohol with something as simple as a probiotic, I knew I had to get the full story.

Picture this: A scientist working diligently in an HIV research lab, struck by a lightning bolt of inspiration. This isn't the beginning of a sci-fi movie; it's Zack's real-life journey as a revolutionary thinker who saw potential where others only saw a dead end. Zack's credentials are as impressive as his ambition – a PhD in Microbiology & Immunology, paired with hands-on experience in clinical trial design, has armed him with the expertise to turn visionary concepts into tangible solutions.

With the company that resulted from his aha! moment, ZBiotics, Zack is carving a new path in the health industry. Launching the world’s first genetically engineered probiotic is no small feat, and the implications are massive. Not only has he opened up a new way to diminish the dreaded hangover, but he's also paving the road for a future where probiotics go beyond gut health, potentially transforming the approach to everyday wellness.

In this episode, Zack and I delve into the science of probiotics like never before. We'll uncover the secrets behind genetically engineering these tiny allies to tackle acetaldehyde, explore the potential future applications of Zack's technology, and maybe even touch on how a classical art & archaeology background pairs with modern genetic innovation. Prepare to look at your morning-after in a whole new light.

During our discussion, you'll discover:

-Zack Abbott…05:35
  • Ben enjoys an organic glass of wine every now and then
  • Endorses responsible consumption of alcohol
    • Even in small amounts, alcohol may cause some issues
  • Zack Abbott worked at a research lab; worked at engineering probiotic strains to help digest alcohol better
  • ZBiotics (use code BEN15 to save 15%)
  • Coming up with the name ZBiotics
  • Zack's favorite cocktail is boulevardier or whiskey-soda

-Is alcohol going to kill you no matter what?…10:31

  • People swearing off alcohol completely
  • Alcohol replacement drinks that technically aren't alcohol
  • For some people, an all-or-nothing solution is not sustainable
  • It’s important to drink responsibly
  • Is alcohol a hormetic stressor?
    • In some cultures known for longevity, alcohol, used in moderation, is an important part of the diet
  • Alcohol consumption is a behavior that goes along with a lot of healthy social interaction
  • Microdosing psilocybin instead of alcohol in social interaction

-What happens when you drink alcohol?…17:11

  • When you drink, you ingest the ethanol, and it goes into your stomach and your intestines
    • It is rapidly absorbed into the bloodstream
    • It goes to the liver for detoxification
    • Ethanol gets converted into acetaldehyde, and then acetate
    • Acetaldehyde is then broken down into acetate
    • Acetate is essentially vinegar
  • It is acetaldehyde that is highly toxic, more toxic than ethanol, but it doesn’t get into the bloodstream from the liver
  • Some of the alcohol that goes into the gut is broken down by the microbiome
    • Not a significant amount of alcohol, but very important in terms of human health
    • That alcohol is converted into acetaldehyde, but then not into acetate like it is in the liver
  • The gut ends up being a major source of acetaldehyde in the body
    • Colonic acetaldehyde levels are 5 to 10 times higher than blood acetaldehyde levels
    • It gets absorbed out of the gut into the bloodstream, and then to the liver
  • Effects of ethanol:
    • Brain – intoxication effects and sleep problems
    • Hormone imbalances
    • Glucose insulin response
  • The more alcohol you drink, the more acid is forming in your gut and going to your bloodstream and liver
  • Other risk-creating elements in alcohol
    • High sugar
    • High-fructose corn syrup
  • People drinking caffeine and alcohol together
    • People are more likely to engage in risky behaviors with that combination
  • Red Bull vodka phenomenon in Europe

-The idea behind ZBiotics…24:43

  • Adjustments to the microbiome to better deal with acetaldehyde
  • The gut is a major source of acetaldehyde
  • The idea that we could deal with acetaldehyde in the gut is logical
  • Zach has a PhD in microbiology – studied bacterial gene regulation
  • Bacteria perform 3,000 biological functions, only some are useful for humans
  • Applying genetic engineering to ensure one additional function to the bacteria
    • They took some safe, edible probiotic bacteria
    • Engineered it to express an enzyme very similar to the one the liver uses to convert the acetaldehyde to acetate
  • The idea is to consume this probiotic before you drink alcohol

-The safety issues of genetic engineering…30:20

  • A lot of people are scared of GMOs mainly because of the way they have been used
  • There's a big debate on the use of GMOs
  • Genetic engineering has no effect on safety 
    • It's just a technology, a tool to make better products
    • A tool that can be used to make both safe or unsafe products
  • Misconceptions about what genetic engineering is
  • Life already alters its own DNA
    • Plant crossbreeding
  • The process of genetic engineering of the bacteria
  • Genetic engineering is just facilitating a natural activity
  • The process does not make the bacteria unsafe in any way
  • ZBiotics provide the bacteria that creates enough of a very common enzyme at the right time and in the right place

-The lack of liver enzyme and the use of antihistamines…35:27

  • The enzyme that the liver uses to convert the acetaldehyde into acetate is mutated in certain people
    • Mostly people with East Asian descent
  • Acetaldehyde Dehydrogenase – enzyme that the liver uses to convert acetaldehyde into acetate
  • Strategene – dirty genes testing
  • Histamine sensitivity:
    • Fermented foods like kombucha
    • Canned fish
    • Alcohol
  • Ben takes ZBiotics (use code BEN15 to save 15%) prior to taking alcohol, glutathione after
  • Ben is not a fan of activated charcoal use after alcohol consumption
  • The volume of activated charcoal pills is too small to have any effect

-DNA in ZBiotics’ probiotic strain…42:20

  • Getting the DNA – the art meets the science
  • Designing DNA suitable for bacteria to integrate into its biome
  • Reading and writing DNA
    • You can just order that strip of DNA to be made
  • Many companies are very good at synthesizing DNA
    • It’s like writing or composing
    • Sticking nucleic acids together in the appropriate sequence
  • How to know it’s safe?
    • The string of letters of DNA is the instructional code for the bacterial cell
    • The code itself does not have any effect on humans
  • Everything you eat has DNA
  • The question is what functions are affected?
  • Many tests for safety are performed
    • Looking at toxicity, allergenicity, pathogenicity
  • It can't mutate you

– Do you need to load the gut with​ ZBiotic ​over time?…48:10

  • Akkermansia by Pendulum (code GREENFIELD saves 20% off your first month's subscription)
  • Podcast with Colleen Cutcliffe:
  • Lactate digesting enzyme
  • Probiotics have to take up residence in our gut
    • That’s difficult because everybody’s microbiome is different
  • No FDA-approved drug that's probiotic-based at the moment
  • Consistency is incredibly hard to gain
  • Most adults do not have lactobacillus in their gut, or at least not in significant numbers
    • The reason why it's a probiotic is because it's a leftover of the dairy industry
    • Not because it's good for human health
  • The bacteria in ZBiotics is Bacillus subtilis (use code BEN15 to save 15%)
    • Is everywhere, and everyone has it
    • Passes fast through the gut
    • Doesn’t disrupt microbiome
    • Produces the enzyme and leaves the body
    • Doesn’t have to load up the gut with it
  • Antibiotics can’t disrupt it because it is not a resident of the gut
  • Zack’s PhD: How bacteria turns on and off different genes in different conditions
  • Engineered this strain of bacteria that was making a lot of acetaldehyde dehydrogenase enzyme
  • Many of the bacteria in your gut are also making it
    • Just not at the right time and in the right amount

-How to take ZBiotics?…54:15

  • It’s a liquid shot, and you take it just before you drink
    • Most beneficial when taken before drinking
  • Stacking a lot of responsible habits and behaviors together
  • When you drink, a lot of things happen in the body
  • The biggest problem is sleep
    • It’s ideal to go to bed sober
  • Alcohol induces a surge of GABA that wears off
  • High-carb meal before bed – you'll go hyperglycemic
    • As blood sugar drops, you wake up in the middle of the night

-Are some types of alcohol cleaner than others?…58:34

  • Fermentation and distillation processes have many byproducts
  • Fermentation affects the flavor in ways that we enjoy a lot of the time, and sometimes don't
  • Red wine has a lot of acetaldehyde
  • People have different reactions to them
  • The cleanliness of the alcohol in general
    • Clear or light-colored alcohols have fewer congeners than darker-colored alcohol
  • A lot of times, it's a personal choice

-Electrolytes and hydrogenated water…1:01:15

  • When drinking alcohol, Ben does the following:
    1. Electrolytes / Minerals / Hydration
      • Because of the increased urination
    2. Hydrogen tablets
      • The anti-inflammatory effect that makes alcohol feel a little bit better
  • Oxidative stress is the body’s response to alcohol
  • Hydrogen gas, in large part produced by the microbiome, is one of the major ways that the body deals with oxidative stress
  • Increased urination is just due to the fact that you are increasing fluid intake
    • Biochemical markers of dehydration are not present
    • Things that make you dehydrated don't feel like how alcohol makes you feel
  • But keeping your blood volume high with fluids is always valuable
  • A study in the Journal of Strength Conditioning Research
    • Compared beer consumption post-exercise with Gatorade consumption
    • Found that beer essentially hydrated you to the same extent as Gatorade with a similar post-exercise recovery boost
  • A lot of studies on rugby players in the 70s who were drinking alcohol after the game
  • The hypothesis that alcohol causes dehydration

-Plans for new products…1:06:24

  • Engineer bacteria to overlay a function that we know is valuable
  • Creating a probiotic that is very specific and tailored to people's needs
  • When ZBiotics launched its first product in 2019, it was the world's first-ever genetically engineered probiotic of any kind
  • Planning to build all kinds of products to do all sorts of things
  • The goal is to make products that basically help people deal with modern life
  • ZBiotics (use code BEN15 to save 15%)

-And much more…

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Resources from this episode:

Zack Abbott:

– Podcasts And Articles:

– Other Resources:

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Do you have questions, thoughts, or feedback for Zack Abbott or me? Leave your comments below, and one of us will reply!

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