TL;DR

Tesseract Life Sciences CMO Ulli Lindauer explains that absorption is the amount of an ingredient taken up into the bloodstream, and it is always less than what was consumed. Bioavailability is the fraction of that absorbed amount the body can actually use. In her example, 100 molecules consumed become 70 absorbed and only four after liver metabolism. CEO Will West adds that peptides are fragile and much larger than typical nutrients, and some have a shelf life of only days or weeks, so a peptide placed in a gummy may be degraded before it ever reaches the consumer.

• Ulli Lindauer describes absorption as the first part of bioavailability: you take x, your body takes up y, and y is always less than x because the ingredient gets degraded.
• Bioavailability is the fraction of the absorbed ingredient the body can actually use. In Lindauer’s example, 100 molecules consumed become 70 absorbed and four after liver metabolism.
• Will West notes that some peptides have a shelf life of only days or weeks before their potency goes away, so a consumer may receive a product with nothing left for the body to use.
• Peptides are much larger than typical supplement nutrients, and the cells of the gut lining can only absorb molecules up to a specific size. Lindauer compares this to a semi tractor trailer trying to fit through a garage door built for a bicycle.
• An injected peptide is exposed to oxygen only briefly. A gummy, by contrast, travels from factory to jar to wholesaler to retailer to consumer and goes through repeated changes in humidity and temperature along the way.

Why is oral peptide delivery harder than standard supplement delivery?

Will West: There are a couple of things. One, peptides are very fragile. Two, they’re much larger than nutrients in the supplement and nutraceutical space. And three, they typically have been used in injectable form, and the market’s trying to expand and gravitate to other delivery systems. Those things make it more challenging to get them into the body, make them ready for the body to absorb, and then ultimately cross barriers to get them into the bloodstream, to the point where they can be utilized by our systems.

The fact that they’re fragile means that they need to be handled in such a way in raw material form to preserve them until they can be put in a format to be used. Even if they’re just used in injectable form, they have to be handled usually frozen or at low temperatures to preserve their shelf life. If you’re trying to put them into a powder form so they could be put in other formats like gummies or melts or strips or nasal sprays, all of which we’re starting to work with through Tesseract, then it’s particularly important that you look at ways to extend their shelf life.

The reason for that is that some of these peptides only have a shelf life of days or weeks before they dissipate and the potency goes away. In those cases, by the time the consumer, the patient, actually gets the peptide, there’s nothing left to be utilized by the body. They’re likely in those situations paying for something when there’s nothing of value there. That’s a massive challenge.

Within that, there are ways of manufacturing that have typically been very popular in the supplement and nutraceutical space, like liposomal, which pose tremendous challenges for peptides. People are trying very hard to use liposomal in the peptide space. But when you combine it with peptides, it’s very counterproductive, and that further exacerbates this problem of shelf life and stability and makes it very hard for consumers and patients to get any value out of the peptides.

This other category, the size of the peptide, is a substantial problem because if you’re trying to deliver it orally, for example, it’s going to go through the gastrointestinal system. A lot of people are looking for oral peptides now or putting them through other delivery systems. Maybe they’re going to be absorbed in the mouth or you’re going to put them in a nasal spray. You have to pass them through a mucus membrane, and the larger the peptide, the more difficult that is. So in addition to whatever the bioavailability of that peptide in the delivery system may be, you’ll want to think about whether there’s a way to enhance the absorption and facilitate passing them through the mucosal membrane.

With every peptide, it’s going to be different because they’re going to pose a unique challenge. That’s something that every manufacturer, every brand, every patient, every consumer needs to think about when they’re trying to understand what they’re working with. There’s a whole host of other considerations. But if you can’t get past those couple of key points, it’s not very easy to have a product that’s going to provide any value whatsoever to the market.

What does absorption actually mean for peptide ingredients?

Ulli Lindauer: There’s a lot of confusion between absorption and bioavailability. Absorption really talks about the amount of an active ingredient, be it a peptide or a nutrient or even a pharmaceutical, that is being absorbed into the body, into the bloodstream. That’s absorption. You take x, your body takes up y, but it’s always less than x, because it gets degraded. This absorption is the first part of bioavailability. Bioavailability is where it matters in the body.

Why is peptide size such a barrier to absorption?

Ulli Lindauer: Absorption is a very big deal specifically for peptides because most peptides are very, very big, which is why traditionally, a lot of people have always believed that you have to inject peptides directly into the bloodstream. If you come with a semi tractor trailer and your garage door is the size for a bicycle (the peptides are the semi tractor trailer, and the bicycle garage door is what your body will allow to pass through), it gets very difficult. The cells in the gut lining in your digestive tract are only able to absorb a specific size of molecule. That’s one of the reasons why it’s not as easy as just putting a peptide in the gummy.

How does a gummy’s supply chain degrade a peptide?

Ulli Lindauer: Peptides are extremely fragile. They react immediately to temperature changes, humidity changes. When you put something in a vial, in a powder, and then put water on it, put it in the syringe, and inject it, it’s only exposed to oxygen and the world for a very brief moment.

If you put it in a gummy in a factory and that thing goes into a jar and that jar is then trucked to a wholesaler, and that wholesaler then sells it to a retailer and the retailer then sells it to the consumer, you can imagine that is a very long journey for this peptide. It’s probably undergone multiple iterations of changes in humidity and temperature, and so it will be completely degraded.

What does bioavailability mean, and how does it differ from absorption?

Ulli Lindauer: Bioavailability talks about what fraction of the ingredient that your body has absorbed your body is then actually able to use. I’ll give you an example. You consume 100 pieces of a very helpful molecule. You absorb 70. Then it goes into your liver metabolism and out come four. You can see how it starts as a funnel, and then depending on what metabolic systems it has to go through, very, very little at the end is left over.

Another example is you take a supplement, or you take an oral peptide. You lose a large percentage of that just on the way to the esophagus, your stomach, the stomach acid, the peristaltic movements in your digestive system. At the end, half of the molecules make it through the gut wall and the other half doesn’t. So there is only a fraction left at the end, and whatever is left at the end, that is usually what is bioavailable.

To make matters worse, there are some ingredients that need an environment of fats or oils or lipids to become bioavailable because they just will not go into the cells if you don’t provide that. Others need other helpers. Some need vitamins. Some need minerals present when they need to be absorbed by the body.

How does Tesseract’s technology address peptide absorption?

Ulli Lindauer: That’s where the Tesseract Life Sciences technology really comes in. We protect each individual ingredient molecule or peptide molecule in a cyclodextrin shell, so that already protects it on its way into the digestive tract. In the digestive tract, we can do a number of different technology approaches, one of which is an absorption enhancer, which allows larger molecules to pass through the gut wall. Another one, in addition to that, is an enzymatic release agent that opens the protective shell at the right place.

That’s why we think our technology is uniquely suited for peptides: protecting them, making sure that they can enter into the tissue or mucosal lining that they’re supposed to go into, and then making them bioavailable.

Edited for length and clarity from a recorded conversation with Will West and Ulli Lindauer.