Back to Blog

Product Safety

A long-form review of the safety of ZBiotics

 

ZBiotics is safe. But we fully understand if you want to dig into the details to be sure. It’s new, which is exciting, but that newness understandably might make some a little anxious. So with that in mind, here’s all the news fit to print about the safety of ZBiotics, in the following sections:

  • Critical thinking: The case on paper
  • Data: 2+ years of testing
  • Engineering: GMO safety generally
  • Compliance: Meeting our regulatory obligations
  • History: In good company

By the way, when we say ZBiotics, in this article we’re talking primarily about the key ingredient: the probiotic bacteria we developed called Bacillus subtilis ZB183 (“ZB183” for short). The other ingredients are water and natural flavoring.

CRITICAL THINKING

The case on paper

What do we need to know about ZB183 to understand it’s potential to be unsafe? 3 questions in particular:

  1. What was ZB183 before being engineered? (What was the “base” it started as?)
  2. What was ZB183 engineered to do? (What changes were made to that base?)
  3. How does ZB183 interact with my body? (What’s going on when I eat it?)

The one-sentence answer to these questions is: ZB183 started as a natural bacteria you likely already eat every day, was engineered to produce a natural enzyme similar to one your liver already makes, and was built to pass through your gut without changing your microbiome or having any lasting effect on your body. There’s no expectation that any of this results in something unsafe. 

Now here are the details…

1. Natural base

ZB183 started out as a naturally occurring good bacteria – one you probably eat every day of your life without even knowing it. The species of that bacteria is Bacillus subtilis (“B. subtilis). B. subtilis is found everywhere – on fresh fruits and vegetables, in certain kombuchas, and in conventional probiotic supplements. 

Humans have been eating B. subtilis for tens of thousands of years. We have even been using it deliberately for centuries to ferment certain foods, the most common example being a Japanese food called natto. Natto is a fermented soybean dish that’s widely considered a “superfood”, largely because of some cool health effects associated with B. subtilis and an enzyme it already produces known as nattokinase, which you can read more about here, here, and here.

Whether you know it or not, you’ve almost definitely eaten B. subtilis before. And in addition to being safe, chances are that it’s actually pretty healthy for you. That’s part one.

2. Natural add-on

Part two is how we took that traditional strain of B. subtilis and altered it. By making precise changes to its DNA, we made it do just one extra thing: produce an enzyme – a natural enzyme that’s in the same class as the enzymes made by your liver every day. That enzyme is called acetaldehyde dehydrogenase (or “ALDH” for short). Its job is to take acetaldehyde and turn it into acetate: something bad into something good.

Your body already produces versions of this enzyme naturally, and there’s no reasonable expectation that the addition of that enzyme to your gut is going to cause any problems. And aside from this added function, the bacteria behaves just the same as it did before we engineered it. That’s part two.

3. Temporary effect

Part three just looks at what the bacteria is expected to do in your gut. Crucially, B. subtilis is adapted to pass straight through your body, without seeding your gut or changing your microbiome. While we don’t have precise measurements on transit time yet, we expect that it takes between 18 hours to a few days to pass through your system, at which point it’s gone! 

This is great, because it means your expectations of ZB183’s interaction with your gut can be consistent across multiple times trying ZBiotics, and you don’t need to worry about a risk that often arises with conventional probiotics: the possibility that they change your microbiome for the bad (a condition called “dysbiosis”).

So that’s the case on paper for ZB183’s safety: it’s the combination of two natural things your body already safely encounters on a daily basis, designed to minimally interact with your body and have no permanent effects. 

But to make sure that the case on paper matches reality, we needed some data from real testing...

DATA

2+ years of testing

We’ve spent the last two years safety-testing ZB183. All of that testing resulted in no observed adverse health effects of any kind. If you really want to dig in, our in vivo data was recently published in the peer-reviewed Journal of Toxicology.

A summary of this and our other testing results is below. 


Test

Result

Detail

In vivo 90-day Rodent Trial*

No observed adverse effects

We performed an experiment in which ZB183 was fed to rats at daily intake levels of 1x, 10x, and 100x expected commercial levels for 90 consecutive days. No clinical signs or adverse effects were observed, resulting in the establishment of a NOAEL of ~10^11 CFU/kg bw/day.  This means we can say that even at 100x higher intake levels than what we plan to market, our product was as safe as water to the rats for the endpoints we observed.

Transferable or extrinsic antibiotic resistance (in silico and in vitro)

None observed

Resistance to therapeutic antibiotics is currently a major public health challenge, necessitating testing for extrinsic/acquired resistance in new products, especially when the relevant genes are associated with mobile genetic elements such as plasmids and transposons, which can be transferred to pathogens or other commensal bacteria. ZB183 was tested for these both by genome sequencing and by phenotypic testing (i.e. testing their growth in the presence of antibiotics), and none were found.

Allergenicity (in silico)

None observed

The sequence of ZB183 was analyzed against a database of known allergens in September 2017, and at that time, no major allergens were identified in the genome. (Please keep in mind, though, that we use soy in the manufacturing process to feed and grow ZB183, so while there should be no soy that makes its way into the final product, you should not eat ZBiotics if you are allergic to soy.)

Unnatural cytotoxicity (in vitro)

None observed

Cytotoxicity is the quality of being toxic to cells, and it can be tested using in vitro methods to determine a degree of cytotoxicity. ZB183 was tested and determined to have no unnatural cytotoxicity.

Hemolytic activity (in vitro)

None observed

Hemolytic activity is observed when a microbe produces compounds that break down red blood cells. ZB183 was tested for hemolytic activity, and no hemolytic activity was observed.

*A note on animal testing

One of our biggest disappointments at ZBiotics has been that to bring ZB183 to market, we needed to conduct animal testing. Specifically, we needed to conduct a 90-day in vivo rodent trial, which used 80 rats and required all rats to be sacrificed at the end of the study. While we felt that the in vitro (non-animal) and in silico (computer) data behind ZB183 were scientifically sufficient to justify safety without in vivo testing, from a regulatory perspective we unfortunately had no choice. We could not launch the product without the in vivo test. 

We deeply identify with those who do not approve. And, of course, we at the very minimum can express our sincere gratitude to the rats. While we appreciate the spirit of the regulations that make in vivo testing mandatory, we are advocates of reduction, replacement, and/or refinement of animal testing wherever it is technically valid and ethically sound. We therefore are advocating against needless animal testing in the regulatory and commercial forums in which we operate.

ENGINEERING

GMO safety generally

Aside from the theory and the data, there is of course always the question of whether the tools of modern genetic engineering themselves – which were used to create ZB183 – carry inherent safety risks above those of conventional breeding techniques.

The answer to that question is no.

Genetic engineering – the technology underlying GMOs – is a tool to make new products. The tool itself does not carry any inherent risk, and it is the resulting products that must be individually evaluated for safety just like anything else. Saying GMOs are altogether safe or unsafe would be like saying that any product made with metallurgy is always safe or unsafe. But of course a sword and a spoon have very different safety profiles. We need to evaluate individual products individually.

With that in mind, the scientific consensus on the safety of the GMO foods currently on the market is settled – having been endorsed time and again by unbiased sources from the World Health Organization (WHO) to the National Academies of Sciences, Engineering, and Medicine.

The WHO puts it this way: “[Genetically modified] foods currently available on the international market have passed safety assessments and are not likely to present risks for human health. In addition, no effects on human health have been shown as a result of the consumption of such foods by the general population in the countries where they have been approved.”

But again, genetic engineering is just a tool, and like any tool it can be wielded carefully or recklessly. That is why we strongly advocate for the extensive scientific evaluation of the safety of all new GMO products as a basic tenet of responsible use of genetic engineering.

COMPLIANCE:

Meeting our regulatory obligations

We wouldn’t be good citizens or responsible stewards of technology if we weren’t adhering to all applicable regulatory requirements related to ZBiotics. So it’s almost a no-brainer to say that our safety and marketability are fully legally compliant. 

But, surprisingly, we’ve found that other companies marketing functional foods, probiotics, and nutraceuticals often cut corners on this stuff. So here it is: a (highly shortened and summarized) list of core regulatory requirements you’ve probably never heard of, just in case you were curious…

FDA requirements for new food ingredient safety.

All new food ingredients (like ZB183) need to be proven safe before they can be released onto the market. We’ve met these through self-certification of Generally Recognized as Safe (“GRAS”) status according to scientific procedures (21 CFR 170.3 and 170.30).

FDA requirements for food-grade GMPs

All food products must be produced according to standards that limit food safety and contamination risks. These are called Good Manufacturing Practices (“GMPs”), and all our manufacturing is done in compliance with them (21 CFR 117).

FDA and FTC labeling requirements

All of our labeling, claims, and marketing language is truthful, non-deceptive, and substantiated with data.

By the way, ZB183 isn’t a dietary supplement; it’s a food ingredient. Curious why? It’s because probiotic bacteria do not, interestingly,  fall into the definition of dietary ingredients (the legal term for supplements) laid out in U.S. law 21 U.S.C. 321(ff)(1)). We think that’s probably because probiotic bacteria, yeasts, and other microbes weren’t as popular as food additives and ingredients when most of the food regulations in the United States were being written. But as that changes, maybe we’ll see a shift…

HISTORY

In good company

Finally, you should know what company you’re in. 

By now, thousands of people have tried and enjoyed ZBiotics. Before launching publicly, we gave out over 5,000 free samples. And we saw no consistent complaints attributable to the product.

Furthermore, we stand by our product’s safety in the most compelling way we know how. Every member of our team drinks ZBiotics, and we share it with our friends and family. Indeed, CEO/co-founder Zack Abbott drinks a bottle out of every batch himself, just to make sure nothing is off and no mistakes are made in manufacturing. He’s now tried ZBiotics over 100 times, without issue. We’re confident in its safety, and our testers and early customers are too. 

BUT, if you have any negative experience with ZBiotics, please let us know. We care about your safety more than anything else. That’s why we did all that safety testing. There’s no hypothesis about any safety problems that we know of, but the world’s a wacky place. So talk to us. We’ll always get back to you.

Liquid error: Could not find asset snippets/subscription-theme-footer.liquid