Dear Friends,

Today, I’m sharing Part 2 of my interview with Jocelyn Bérubé, who is the Executive Vice President for Scientific and Regulatory Affairs at innoVactiv regarding collagen.

In Part 1, Jocelyn provided detailed answers to many misunderstood or confusing collagen supplement topics and questions – while also highlighting the unique attributes about the exciting new marine-derived Cartidyss collagen ingredient.

In Part 2, Jocelyn breaks down the science and potential skin, hair and nail benefits of Cartidyss:

Carl: So let's turn to some of the results that users experienced with respect to skin — reducing the appearance of wrinkles, improving hydration, or the overall appearance of the skin. You published a study in the journal Molecules a few years ago. Can you give us a little overview of that study in terms of how it was structured and what they investigated?

Jocelyn: Sure. The study was aimed at testing the effect of a daily dose of 500 milligrams of Cartidyss, taken in the evening, on signs of aging after three months of use. They recruited 46 healthy women from 45 to 59 years of age; the average age was 52. Overall the study was very well conducted because it was randomized, controlled against placebo, and double-blinded.

So neither the investigators nor the participants knew what type of product they had. That makes sure everyone is evaluating the product without knowing what they're taking. And they were also making sure every participant was comparable — for example, applying sunscreen every day so that they would avoid interference from exposure to sunlight. So there were a lot of control methods within that study that made it particularly strong.

Carl: You mentioned they were instructed to take the supplement at night. Is there anything specific to that, or was it just for convenience, a standardization purpose?

Jocelyn: Yes, just for convenience. Since it is one dose per day, you can actually take it at any time. We're not talking about a large amount. When you're taking 5 to 10 grams of protein as part of a collagen supplement, it can start to have an impact on your appetite, because that's a fair amount of protein. With Cartidyss, that's not something you'd expect. So you can take it before meals or at night. In this case, they had to pick one, so they chose to go at night.

Carl: Fair enough. So obviously, women and men in their 50s are interested in reducing the appearance of wrinkles, so maybe we'll start there. What were the results with Cartidyss?

Jocelyn: Well, that was one of the main takeaways of this study — to look at wrinkles around the eye, around the mouth and nose, and also on the forehead. To do that, they used a grading system. They evaluated the wrinkles visually, all done by a trained dermatologist, and they had to grade the wrinkles from one to five — one being baby skin, and five being more prominent, visible wrinkles.

The average score was actually reduced by 31% around the mouth and nose area, which was very significant. They had a 26% reduction in the crow's feet area, and a 14% reduction on the forehead after 90 days. So in terms of reduction in the appearance of wrinkles, definitely something you can see. And there are before-and-after pictures and everything, so it's really something very strong as an impact from that clinical study.

Carl: So you said 31%, and I guess that's this nasolabial area here — that fold, that crease between the mouth and the nose?

Jocelyn: Yes, exactly.

Carl: That sounds like a pretty high number. I don't know that I've seen that with other collagen ingredients. Is that your understanding too?

Jocelyn: That's my understanding too. These are actually very strong results. The behavior may be the same everywhere — you have that overall rejuvenation effect on the skin — but the statistics and methods made it reach a significant level for the mouth and nose as well as the crow's feet area. The reduction on the forehead was not significant.

Carl: Right. It was 14%, but that didn't reach significance compared to the placebo. And that was 90 days, you said, or 60 days?

Jocelyn: 90 days.

Carl: 90 days. Now, I remember from reading the study, they also used some high-resolution imaging technology to do a couple of things, including measuring the density of the dermis layer — the skin layer right beneath the epidermis on the outside. How does that affect skin appearance and were the results notable, in your opinion?

Jocelyn: Well, the results were fabulous. When you look at skin density, what you're talking about is the fibers, the fiber networks, the proteins that support the skin structure — really the collagen network, the elastin network — and that's what we need to promote. So that was also a primary endpoint for the study.

To evaluate it, we use an ultrasound technique. If the skin is very loose, there's a low density — basically a dark area, like there's nothing there. Whereas if there is a very high-density network of proteins, then the ultrasound bounces back and gives a high-density signal.

So what we were able to obtain in this clinical trial is that the use of Cartidyss induced a 38% increase in skin density compared to placebo. That can convert into 38% more fibers — more elastin, more collagen fibers — that help support the skin structure. And that same ultrasound probe also looked at dermis thickness, which is a sign of hydration. So density is one part, but thickness is the second part.

In this case, we saw a 10% gain in hydration, but there was a 12% decrease in the placebo group. So in terms of net gain, it's about a 22% gain of hydration with the use of Cartidyss in this clinical trial.

Carl: That's another impressive result. So if I understand you correctly, you have the density, which is just measuring the number of fibers present — collagen and elastin fibers. Is that right?

Jocelyn: Yeah, to sum it up, yes — this is basically what supports the cells.

Carl: Okay, and then you have the thickness of that network, essentially, which helps lock in the moisture. Is that the way to think about it?

Jocelyn: Well, the dermis actually has components that capture water as it travels through the skin. The more GAGs you have, the more capacity you have to capture that moisture and to have better-hydrated skin. So promotion of GAGs is one of the features. But then what we observe as a result is that those GAGs, when they are hydrated, swell and gain volume. And that's where you have that increased thickness, because you have those swollen glycosaminoglycans — they've taken up some water and they're now like a full sponge rather than a dry one within the skin.

Carl: And again, for the audience — remember the GAGs we're talking about are things like hyaluronic acid, chondroitin, and glucosamine. Those are the things that help contribute to the hydration of the skin. Did you look at skin smoothness and texture?

Jocelyn: Yes, we actually looked more at pore size, for example. That's a very important aspect of skin surface appearance. To evaluate pore size, it was all done by automated software that looked at imaging, found the outline of the pores, and was able to count how many pores of each size category there are.

What we noticed is that there was a very great reduction of large pores in the treated group — 19% fewer large pores. At the same time, there was a 14% increase in the placebo group. So basically, over the course of the study, there was a great and increasing difference between the two groups, in favor of much smoother skin appearance for the treated group.

So you could have much softer and more uniform skin after using Cartidyss. They also looked at skin through a very specialized kind of microscope called a reflectance confocal microscope. It's very complex, but it's a tool that helps you see the collagen fibers within the skin of your volunteers — you're basically able to see the molecular structures of the fibers. What they saw through that tool is that there was a lot of disrupted collagen in all participants at the start of the study.

Picture a collagen fiber like a cord between two anchors: if it's broken, the cord will just coil or curl itself up. So they noticed these kinds of disrupted collagen in the skin of every volunteer at the beginning of the study. What we noticed at the end is that all the volunteers in the treated group were completely rid of those broken collagen fibers — they had been replaced partially by functional fibers.

So instead of a broken rope, now you have a complete cord, a complete fiber of collagen. And none of that happened in the placebo group. So it was very impressive to see how the product can help replenish the skin with functional collagen rather than broken ones.

Carl: That's great. So I just want to go back to the impact on the large pores. If you have a higher concentration of larger pores, does that mean your skin's going to probably be rougher and less smooth?

Jocelyn: Oh, yes. That's what you see for aging skin — pore size is almost correlating with aging. So this is a very important surface aspect of the skin that you want to improve: pore size.

Carl: I know you guys have done some other mechanistic studies on what Cartidyss is doing to support all this. Did that tell you anything noteworthy?

Jocelyn: Actually, the mechanism of action is, I think, very interesting. We used an award-winning, groundbreaking human protocol to look at these aspects of mechanism of action, as well as bioavailability, all in one human trial. This is very unique, because in this type of protocol, we have healthy volunteers who take the product orally, just like a supplement.

So they ingest Cartidyss and have the opportunity to digest the product, and then you can see in the bloodstream the pace at which some metabolites of the product make it into the bloodstream — that's where it needs to be to be effective. So that first part of the study is essentially feeding the subjects with the supplement, and then you take blood samples at different times to see where the peak concentration is.

In terms of Cartidyss, the test showed that we had an increase of 88% in hydroxyproline, which is one of the markers of collagen — so 88% more hydroxyproline after 140 minutes. And we also had 24% more chondroitin at that same time. So it peaked a little bit after two hours in the bloodstream; all the metabolites from Cartidyss are now absorbed.

That takes us to the second part of the study. So first part: we know the product gets into the bloodstream — that's what we claim. But then in the second part, we take that blood sample and apply the absorbed metabolites to human cells. We get some skin cells — we could test any type of cells, but in this case we use fibroblasts — and we put them in culture. We can expose these cells to the blood of our volunteers, either before they used the supplement or at the peak concentration of metabolites.

So we're able to see, compared to baseline, what the impact is on skin cells exposed to the metabolites of Cartidyss. What we found is that the skin cells exposed to these metabolites produced 40% more elastin fibers than the cells exposed to the blood without Cartidyss. So there was a great impact on the metabolism and the production of those fibers. And there was also an impact on hyaluronic acid production — a 5.5% increase. So in terms of hydration gain, for example, that's what we also show here in terms of mechanistic support. So this is all showing how we can help improve skin turnover and improve skin support.

Carl: I know you guys did a consumer study, which involved 75 French women who were younger, between the ages of 25 and 50, if I have that correctly. Obviously different from a controlled environment where you do a placebo-controlled randomized study, but the findings were, I think, pretty similar to the published study in Molecules. And interestingly, there were also some very notable effects reported for not only skin, but hair and nails too. So in your opinion, what were the key takeaways from this study?

Jocelyn: I really like that study — obviously not as a single piece of evidence; you don't rely on consumer data alone for complete scientific development. But when it comes as a supporting piece of evidence on top of a well-structured, randomized clinical trial, it's always good to have, because when we use supplements, we never see what our life would be without using them. We never see the placebo side of things; we always see the treated side.

So getting that type of data from real-life use of the supplement is always interesting, to actually document what people feel when they use the product. As you mentioned, we had that study — 75 people, 25 to 50 years old, for three months. So they were not really advanced in their aging process, but there were still improvements. And as you mentioned, you want people to start using the product more as a preventive rather than just trying to fix something.

They used the product at 500 milligrams a day, so a very similar intake regimen to the randomized, placebo-controlled study. We looked at their appreciation of the product after one, two, and three months — we also looked at earlier time points — and to see if there were benefits beyond skin, as you mentioned, maybe some benefits for hair and nails. So we looked at that overall aspect. We took some baseline measurements of how much they appreciated some aspects of their bodies — their skin, hair, and nails.

The most common concerns for people entering the study: their hair being dull and thin, their nails being brittle, sagging skin on their face or body, dull skin on the face, or facial lines and wrinkles. Some complained about orange peel — we'll see about that later, whether we did something good on these complaints. But in terms of findings, they were actually very, very positive, even after only 30 days of use.

In terms of consumer appreciation for their overall hair, skin, and nails, it went from an average 12% to 20% at the beginning — so they were very rough with themselves; they really didn't like their hair, skin, and nails overall — but after 30 days of treatment, they went up in appreciation to 74% to 86%. So a very huge, drastic improvement in their self-perception. In terms of comments, people noticed their hair becoming shinier, nails becoming stronger, and better skin complexion. Overall, they were very happy with the progression.

And that positive feeling continued to grow, almost to 87% to 90% after two months, and remained stable for the third month. People said they had more hydrated skin, stronger hair without split ends, and shinier nails. So when you look at the overall study, you can see that Cartidyss actually relieved all of the common concerns of participants — except for the orange peel. It did nothing for that. But it's good to see that it's not a magic bullet; it doesn't do everything, but it did work on all of the major and common concerns. Most people were very happy with the use of the product.

Carl: It's great data. My one question for you is with respect to the strength and appearance of nails. I know that's more of a benefit we've seen with taking keratin protein. Has that been something seen a lot with collagen too? I just can't recall.

Jocelyn: I haven't looked at collagen on a specific aspect for nails, but I saw that some supplements that help support the strength of the fibroblast network can also support their production of keratin. So that could be some element to bring to it. But this is all new science in terms of the mechanism for nails with Cartidyss — this is really just the beginning of something. We're seeing some of those benefits that are felt by users, so it may be the beginning of a new project for us as well.

Carl: I was curious about how long it takes to start seeing benefits with Cartidyss. And then usually, when you start, it's not the end; the results typically improve with continued use, and certainly you'd hope you sustain some of those benefits too. So how would you summarize that?

Jocelyn: Well, there's obviously strong support for using it for the full period of 90 days. You get the full benefits and the full experience from using the product. But what we get from consumer data is that you start to see those results earlier. And it's not surprising after 30 days, because this is the actual skin renewal rate. At a young age, in your mid-20s or 30s, you have that skin renewal that happens almost once per month. Obviously this starts to slow down as we age — the rate of renewal slows.

So if you're 60, you may need to use the product for two months before you start to see this, because the time for your skin cells to renew is slowing down to about two months. And keep in mind that collagen production, and its turnover, is a dynamic process. Our skin never stops making new collagen, and our body never stops making new collagen. So if you stop using the product at some point, there will be a certain time during which you're still drawing on accumulated collagen.

But with the turnover and the downfall of your collagen production, you'll probably fall back to losing the efficacy upon stopping. That should probably last you for a few weeks before you start to notice some effects from stopping.

Carl: That makes sense. And I really appreciate the clarification on middle-aged-to-older folks: skin turnover takes longer, so hang in there. If you're not seeing anything — if you don't think you're seeing benefits after 30 days — give it 60, and certainly 90, because when we talk about these results, we're talking about averages, right? Some people can see results quicker; others are just going to take longer for you to get the full benefit.

Jocelyn: Of course. And if you're exposing yourself to the sun without protection, you're breaking down more collagen as well when you do that. So personal behavior can also have some impact on that.

Carl: Absolutely. has the research, or any of the lab data you've done, highlighted any safety concerns or precautions those thinking about using Cartidyss should be aware of?

Jocelyn: No, actually there were no side effects recorded during our clinical trials, and none in our consumer trials either. In terms of collagen in supplements, there are some complaints about gastrointestinal symptoms, such as bloating or heartburn sometimes, but that's usually associated with a high level of intake. We have a very low effective dosage, so that's another advantage of choosing Cartidyss — you're less likely to have those types of side effects because you're using a much lower dosage, and the product is also very easy to digest and absorb.

So all in all, we think there is absolutely no challenge or risk for side effects. The only limitation, in my perspective, is that because it is a fish-derived collagen, obviously if someone is allergic to fish, they should not be consuming this product. I know your labels will show the presence of fish, so there's no worry about that, but that would be my sole contraindication — for people who are allergic.

Carl: No, it's great advice and I appreciate the detail on that. We covered a lot. What else should consumers know about Cartidyss that we may have missed?

Jocelyn: I think Cartidyss actually packs a lot of impact into a very low-dose product. If you're looking for something convenient and effective, this is definitely the product to go with. There are a lot of advantages to using our product over other collagen — it's more practical. The fact that it is hydrolyzed to small peptides enhances bioavailability and digestibility, it's more effective, and it makes sure you don't risk any digestive upset.

We've shown a complete turnover of the skin support structures and fibers — the renewal of collagen fibers, the promotion of elastin fibers, the benefits on hydration, on wrinkles, on firmness. Those are all ranges of benefits that can be experienced by users, and I'm sure they'll see results on hair and nails too. In terms of sourcing, we have sustainability; we have a great product, a great process.

The product is clean and virtuous because we're making it from byproducts of the fishing industry. So in a nutshell, it's good for you, it's good for the planet, and it's good for local communities. So I think it's a win-win for everyone.

Carl: Couldn't agree more. We appreciate you taking the time to tell us the full story.

Jocelyn: Thank you, Carl.

That concludes our interview – hope you found it helpful. You can also read more about Cartidyss on the TrueNuGrow+ product page.

Yours for Good Health,

Carl Pradelli

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