Show me the science.

Our mission at ZBiotics is to use science to solve life's everyday problems. We believe that true science still means being transparent: admitting what you know and what you don't know. That is what we're doing here.

What follows is a description of the scientific background to our first product.

What is a hangover?

The word “hangover” can mean a lot of different things to different people, as we’ve found, and from a scientific perspective, this fact isn’t surprising. What is commonly referred to as a hangover is actually the convergence of several different things happening all at once as your body is exposed to and tries to metabolize alcohol. In brief, this is an oversimplified and not at all comprehensive list of the things that might be happening in response to alcohol that could result in you not feeling tip-top the next day:

1. Alcohol negatively affects the quality of your sleep, causing grogginess and daytime sleepiness (Citation)

2. Alcohol irritates gastrointestinal (GI) tissues and causes inflammation that can result in discomfort and other GI distress. (Citation)

3. Alcohol alters and disrupts the balance of your microbiome — the massively complex and ever-changing community of microbes that live in your gut — potentially causing bloating, gut and systemic inflammation, and other GI distress. (Citation)

4. Alcohol inhibits anti-diuretic hormone and causes increased urination and decreased water recycling, which can lead to mild dehydration. (Citation)

5. Congeners — byproducts of alcohol fermentation and production that are present in small quantities — can cause all sorts of undesirable effects (Citation). The list of congeners is long, and the effects are varied.

6. Alcohol is converted by enzymes in your liver into acetaldehyde and then by different enzymes into acetate. The intermediary acetaldehyde is a known carcinogen that wreaks havoc on your body. It is known to cause DNA and cellular damage, inflammation, and results in some seriously nasty symptoms if your body is exposed to enough, such as nausea, vomiting, tremors, dizziness, diarrhea, and malaise. (Citation, citation, citation.)

7. Alcohol is converted by enzymes and microbes in your gut into acetaldehyde, but far less of this acetaldehyde is converted to acetate than in your liver. This is the major source of acetaldehyde exposure in your body. (Citation)

And as we said, this is only the beginning of the list. There are lots of scientific studies demonstrating all kinds of other responses your body has to alcohol that can also impact the way you feel the next day. So the point here is that a “hangover” is dictated by a crazy complex network of effects and bodily responses that vary from person to person and night to night based on limitless mixtures of each of these responses in a given set of circumstances. As such, anyone who claims they have a “hangover cure” is almost assuredly lying to you (which you might think sounds strange coming from me, but bear with me). You can probably see that to solve all of these problems simultaneously would require a pretty amazing and complex solution, and quite frankly we don’t even understand the problem well enough to come up with something complete.

However, we can chip away at it. BUT that doesn’t mean oversimplify it.

Why the current “solutions” don’t make sense.

A hangover is not just dehydration (and in fact it probably has very little to do with dehydration: citation). A hangover is not just poor sleep. A hangover can’t be simply fixed by giving your body molybdenum, or vitamins or random plant extracts that “help your liver”. If there was a plant that prevented a hangover, someone would’ve found it at some point in the thousands of years of human history that we’ve been intentionally consuming alcohol. No one is going to stumble across a plant for the first time in 2018 that miraculously fixes a hangover. Oh, and the activated charcoal thing, which is supposed to “filter your blood” or whatever, has been shown to be a complete myth (Citation), so don’t waste your money there. (We’d like to discuss each of the ingredients on the market today, but we’ll save that for an organized chart to be posted in the future, and keep moving forward for now).

No, to solve a problem as complex as a hangover, something new has to be invented. To have any impact at all, something has to be built from scratch to purposely address one or more of the known root causes of people’s experience of a hangover.

So where do we start? At ZBiotics, we decided to start with acetaldehyde.

Acetaldehyde.

Acetaldehyde is a known byproduct of alcohol metabolism, and we have a wealth of convincing data showing that accumulation of this molecule can result in a seriously crappy next morning! It is super toxic and far more misery-inducing than alcohol itself. And to-date there really isn’t anything out there that sufficiently addresses it. The closest thing is cysteine and cysteine derivatives, such as N-acytl cysteine (NAC), which have been shown to bind to acetaldehyde and potentially reduce one’s exposure. However, these interactions are reversible, meaning that they are continually binding but also UNbinding from acetaldehyde, and each individual molecule of acetaldehyde has to be bound by an individual molecule of cysteine, so cysteine has to be present exactly when acetaldehyde is, and in high enough concentrations all the time so as to make the binding favorable and likely. Sounds imperfect? It is, and the efficacy has been limited at best.

Other small molecules and hangover products claim to also break down or remove acetaldehyde, but they don’t. For instance, one of the new hot molecules in the hangover space is called dihydromyricetin (DHM), which comes from the oriental raisin tree and is sometimes alternatively referred to as oriental raisin tree extract (the names are not precisely interchangeable, but we won’t bore you with details). Weirdly, some products claim that DHM removes acetaldehyde, which just isn’t true. There is definitive data to show that it has no effect on acetaldehyde. And we say “weirdly” because DHM has been show in small clinical studies to have other positive effects, such as inhibiting alcohol’s effects on GABA receptors (Citation). Why claim that your molecule does something it doesn’t if you actually have science to back a different claim?! Probably because reducing acetaldehyde is a much better claim than reducing your experience of alcohol itself…

We decided that a better solution than small molecules and plant extracts would be to deal with acetaldehyde the same way your body already does. Rather than try to bind it up, we wanted to actually break it down into acetate (an innocuous molecule, essentially vinegar) like your body does. This requires an enzyme.

Enzymes.

Enzymes are proteins that can do a function. For example, you’re probably aware of the sugar in milk called lactose. Your body makes a protein called lactase, which is an enzyme with the function of breaking down lactose. People who lack the ability to make this enzyme can get sick because they can’t break down lactose. They are called “lactose intolerant”. Analogously, pretty much everyone is “acetaldehyde intolerant”. We do have enzymes (called acetaldehyde dehydrogenases) that break acetaldehyde down, but we don’t have enough of them in the right places to handle the amount of acetaldehyde we can be exposed to when we drink alcohol (probably because we didn’t evolve to drink alcohol). So when we are exposed to it, we get ill.

Stick diagram of an acetaldehyde dehydrogenase enzyme

So ZBiotics thought, why not give people an enzyme that breaks down acetaldehyde, and specifically in the place it’s needed most: the GI-tract, where it accumulates in the highest amounts. Unfortunately, in most cases you can’t just make an enzyme and give it to people to eat. As we said, an enzyme is a protein, and most proteins you eat get broken down very quickly as food for your body. There are a few exceptions to this rule (notably, actually, the lactase we discussed above is a rare exception that is extremely robust and stable and can pass through your stomach acid and gut environment and still stay functional), but mostly if you want to deliver a functional protein to someone, you have to inject it, like insulin.

A bioengineered probiotic.

So, rather than give people the enzyme itself to break down acetaldehyde via injection (which would be crazy), we decided to engineer probiotic bacteria to make the enzyme directly in your gut. The species we use — called B. subtilis — is safe (you likely already eat it everyday of your life) and naturally has the ability to pass through your stomach acid unharmed and make enzymes in your gut (Citation). This solves the huge problem of keeping the enzyme stable in your GI-tract. So nature got us 90% of the way there already (thanks nature!). Then it was just a matter of engineering B. subtilis to express lots of the specific enzyme you need to break down acetaldehyde.

For that, we spent two years in the lab building a solution (background: I, Zack Abbott, am a PhD microbiologist who has spent the last 10 years developing expertise in bacterial genetic regulation). We started by building a strain of B. subtilis that is capable of always (regardless of conditions) expressing lots of a super-efficient version of an enzyme that breaks down acetaldehyde. The idea is that if you eat this bacteria, it will naturally pass through your stomach acid and get into your gut. Then it will go about its normal business as it passes through your intestines, with only one significant change: it will also express lots of the enzyme that breaks down acetaldehyde. So if it encounters any acetaldehyde while it’s passing through your intestines, it will hopefully break it down into acetate.

The ZBiotics hypothesis.

We say “hopefully” because we don’t know yet if it will do that. We DO know for certain that the bacteria I engineered are excellent at breaking down acetaldehyde in a test tube. We are still in the process of gathering data on whether it can break down acetaldehyde in your gut. We don’t think there should be any difference, but we are scientists, so we don’t promise things we don’t have real data to back up. Until we complete our studies, we can’t say for certain our product will remove acetaldehyde from your gut. We also can’t say for certain that if we DO remove acetaldehyde from your gut, it will result in you feeling any better. Therefore, we’re also in the process of gathering data on that! But hopefully we’ve convinced you that at least in principle our hypothesis makes sense:

1. Known: Acetaldehyde is bad and is known to cause some really nasty symptoms of a hangover (Citation)

2. Known: Your gut is a major source of acetaldehyde (Citation)

3. Hypothesis: if we remove acetaldehyde from your gut using a logically designed and novel scientific solution, we can positively affect the way people feel the day after drinking.

But, we do think this product has a high likelihood of success! As such, we wanted to get it into people’s hands as soon as possible to try it out for themselves. So while we work on crossing all our T’s and dotting all our lowercase j’s on the data side, we’re simultaneously working hard to get people out there trying it as soon as possible!