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Native type II, hydrolized, undenatured: There’s a variety of different collagen products available on the market, but how do they differ? More importantly, how do they help formulators respond to trends in the growing mobility market? Answering these questions and more, this webinar focused on demystifying the use of collagen for joint health products, ranging from understanding terminology to knowing the difference in the mechanism of action. Scientific data and evidence of the efficacy of native collagen Type II were also discussed, referencing Bioiberica’s native Type II collagen - b-2cool®.
Good afternoon everyone.
I'd like to warmly welcome all of our global listeners to today's webinar.
My name is Lakshmi Haig and I'll be moderating your webinar today.
I'm the deputy editor of CNS Media, which is a publisher of The World of Food Ingredients, Food IngredientsFirst.com, and NutritionInsight.com.
We are a leading media agency in the B2B food ingredients and nutrition space and sister company to Enova Market Insights.
Today, Nutrition Insight is hosting the webinar entitled Polon for Joint Health Understanding its Forms and Uses, which is sponsored by BioE Vrias.
This webinar will focus on demystifying the use of collagen for joint health products, from explaining terminology to outlining the differences in the mechanism of action.
On the market, we see native type 2 collagen, hydrolysed collagen, and under-natured collagen.
There's clearly a variety of different products available, but how do they differ?
That's the question.
And more importantly, how do they help formulators respond to trends in the growing mobility market.
Scientific data and evidence of the efficacy of native collagen type 2 will also be discussed today.
Referencing Baoerrica's native type 2 collagen, B24 in particular.
But first, I'm going to lay out some market data on the collagen space as a whole, based on analysis from an open market insights.
This can give us a deeper insight into the market behavior of the ingredient in the in the past years.
So, if we go to slide one.
We see that the collagen market is really growing and diversifying, with data illustrating that it's really an exciting time.
You can see here how supplement launches with collagen are on the rise.
From 202017 to 2019, there was a 14% increase in launches, for example.
However, what's really interesting here is that supplements with collagen that also featured a joint health claim actually saw a bigger increase of 22%.
So this shows us that joint health is really a strong, a strong claim for the collagen market as demonstrated by the statistics.
And, and it's also something that is really communicated front of pack, and we can see that in the example here on the right.
Now, the growth of the ingredient isn't localized to just one geographical area, and it's really seen a, a surge in global interest.
As you can see in this global overview, launches featuring collagen are growing in multiple regions.
Such growth is driven by a growing body of research on collagen's efficacy for skin and joint health, among other drivers.
Australasia has seen a particular uptake in launches, a massive growth of 52%.
So this really contrasts the data for the Asian market, for example, and we can see here that that has seen a decline of 8%.
But we have to remember in Asia, the use, the use of collagen and supplements has been established for quite some time.
So this can explain why it's not seen such a large jump in launches in recent years.
This slide gives gives us an overview of the top positioning companies are using to market their collagen substances to consumers.
Now, although skin health claims came out on top, joint health claims actually experienced the highest growth between 2014 and 2018.
So although collagen is a key ingredient in the concept of beauty from within, which is really gaining traction in traction in the market, it's its role in joint health appears to be even more in demand.
We can see that this space is ballooning right now as mobility and joint health supplement users are getting younger.
This is because consumers are taking a more preventative approach to aging and we really see this gaining traction in the market.
Now, as mentioned before, the collagen market is diverse, but the data shows that the fastest growing collagen is type 2, despite hydrolysed collagen being the most used ingredient.
This indicates exciting times for type 2 collagen.
Now this last slide shows that although collagen supplements come in a range of formats, the tried and tested capsule format is experiencing the highest growth.
As illustrated in the examples, such such capsules are being launched in global markets from Singapore to Brazil and the US.
Now to wrap it up another market insights, it's time to introduce our speakers from Bao Eberria.
So firstly, Doctor Daniel Martinez Pooch is head of late development and product support at Biorica with a doctorate in veterinary medicine, a PhD in nutrition, and a master's degree in animal science.
His main lines of research are joint health, metabolic syndrome, and cognitive health.
Our second speaker is Monica Gomez Nevado.
Monica has a background in science and marketing, with a masters in pharmaceutical marketing, and two bachelor degrees in marketing and psychology.
In her role, she's responsible responsible for Bayoerrica's branded ingredient portfolio for joint health.
OK, so as we continue the webinar, we also encourage our listeners to send in their questions, and we'll address you at the end in a live Q&A session.
OK, now, over to you, Monica.
Hello, everyone.
I'm Monica Gomez, and I'm product manager in the healthcare division at Bio Iria.
Joining me today is Doctor Daniel Martinez Puch, head of late development and product support at Bio Irica.
The aim of our webinar is to demystify the use of collagen for joint health products, which includes understanding terminology and exploring the different mechanisms of action.
We will focus on the use of native type 2 collagen, looking at the scientific evidence of B2C, bio varicose native type 2 collagen.
Before we start, just a brief introduction about our company.
Biorica is a global life science company committed to improving the health and -being of people, animals, and plants.
We specialize in the identification, extraction, and development of biomolecules for the pharmaceutical and nutraceutical industries, including collagen.
This specialization has positioned us as the leading heparin API manufacturer and a world reference in other naturally derived APIs and ingredients such as chondroitin sulfate, hyaluronic acid, native type 2 collagen, and thyroid.
Since the foundation of the company in 1975, Bayo Iberrica has consolidated its position as an expert in joint health and mobility thanks to a constant commitment to science and research.
Our portfolio includes a range of innovative and widely researched health ingredients for joint health and mobility, including our native type 2 collagen, B2C, which we will discuss in more detail later.
The collagen market.
Collan can, can be commercialized in the form of gelatin, hydrolyzed collagen, or native collagen.
Key applications include joint health, beauty and cosmetics, bone healing, and food and beverage.
The global coton market is growing.
It is estimated to reach 4.3 billion by 2024 with an aggregated compound annual growth rate of 5%.
Colagen is widely used for joint health and is rapidly gaining market share in this category of products, historically dominated by ingredients such as glucosamine and chondroitin.
According to the Nutrition Business Journal, US sales of dietary supplements containing collagen increased by 30% in 2018.
This growth represents a very interesting business opportunity for dietary supplement manufacturers.
One of the reasons why collagen market is growing so much is consumer knowledge.
FMMG gurus surveyed 25,000 consumers in 25 countries, and 48% said they have heard about collagen as an ingredient.
And what about consumer perception of the different joint healthy ingredients?
As you can see in this graph, consumers are more willing to pay a premium price for products containing hyaluronic acid and native collagen type 2.
Less are willing to pay a premium for products containing collagen, glucosamine and chondroitin, fish collagen, and eggshell membrane.
Now, Doctor Daniel Martinez Booch would talk about the science behind collagen in joint health, and more specifically about the scientific evidence of B2C, bioarria's native type 2 collagen.
So what are collagens?
Collans are the most abundant family of proteins in the extracellular matrix of connective tissues.
They have a variety of important biological functions.
Among them, the most known is its structural role.
According to the 3-dimensional shape, 28 different types of collagen have been described.
At the cartilage level, type 2 collagen is the most predominant.
Its role is to provide tensile strength and firmness to the tissue.
As a treatment orally taken, there are 2 types of collagens used in the commercial products.
There's the native type 2 collagen, which is a natural form of collagen, preserving the biological, biologically active form of the molecule, a quaternary structure consisting of a folded triple helix of long polypeptide chains.
On the other side, there is the hydrolyzed collagen, consisting in a mix of church chain peptides obtained after the collagen has been digested and the triple helix is broken.
To better understand collagen products, it's important to point out the main differences between the two forms of collagen that could be found in the market, native and hydroly.
First of all, native collagen maintains its three-dimensional structure.
On the contrary, hydrolyzed collagen is subjected to a digestion process, and it consists in a small collagen peptides.
Regarding the type of collagen, native collagen is mainly based on type 2 collagen, whereas hydrolyte collagen comes from a mix of different types depending on the origin.
However, it should be noted that the type of collagen is defined by the structure of the protein, and in hydrolyzed collagens, the structure is lost.
So regardless of the type of origin, hydrolyzed collagen is a mixture of small peptides and amino acids.
Furthermore, the natium form does not require absorption to elicit its effects, while hydrolyzed collagen needs to be absorbed and reach the cartilage in order to be effective.
This is because native type to collagen works through a specific immune-mediated mechanism of action called or tolerance.
In contrast, hydrolys collagen peptides favor cartilage production, acting as building blocks.
Differences in mechanisms of action explain differences in daily doses of both products, being 40 mg for native collagen and up to 10 g for hydrolyse.
So, but what is oral tolerance?
Oral tolerance has been classically defined as the specific suppression of immune responses to an antigen by prior administration of the antigen by the oral route.
In the case of osteoarthritis, the oral administration of type 2 collagen suppresses the immune response against joint cartilage that contains.
Endogenous type 2 collagen.
The question is why there is an immune response against type 2 collagen in osteoarthritis.
The fact is that it has been demonstrated that cartilage damage results in the release of type 2 collagen fragments.
These fragments are recognized as auto antigens and generate an immune-mediated inflammatory response against articular cartilage, thus aggravating the osteoarthritic process.
In consequence, the suppression of this process by oral administration of type 2 collagen leads to cartilage protection and clinical improvements.
But how exactly does native collision work?
So early taken native collagen, reach the base patches in the small intestine, where is recognized by the immune cells associated.
The payer patches are lymphoid follicles responsible for immune surveillance of the intestinal lumen.
They activate or deactivate the immune response against foreign substances.
In the Bayer's patch, native collagen is recognized by antigen-presented cells, the dendritic cells, and binds to them.
Afterwards, they interact with T lymphocytes and generate regulatory lymphocytes called T-rex.
These lymphocytes leave by your patch, enter into the systemic circulation, and suppress the systemic immune response against type 2 collagen.
So what is B2cul?
B2cul is a natural ingredient developed by Bioverica containing native cytokolagen.
The native type 2 collagen is extracted from chicken sternum cartilage using a strictly controlled process that ensures type 2 collagen to maintain its native form, the the biologically active structure of the collagen molecule.
The main structural protein in the cartilage and provides tensile strength and toughness to the tissue.
Some joint disorders involving inflammation and cartilage erosion are caused by an immune response mediated by the endogenous type 2 collagen fragments, among others.
B2 cool is a natural product supplying native type 2 collagen.
The strictly controlled extraction and manufacturing process of B2 cool ensure type 2 collagen to maintain its native form, the biologically active structure of the collagen molecule.
Thanks to preserving its native form, B2.
Cool works through an immune mediated mechanism of action called oral tolerance.
It consists of a diminished immune response to a previously administered substance.
When orally taken, B2 cool passes through the stomach without being denatured and reaches the payer's patches in the small intestine.
Payer's patches are lymphoid nodules responsible for immune surveillance of the intestine lumen.
They activate or deactivate the immune response against foreign substances.
In the payer's patch, B2C is recognized as native type 2 collagen by the immune cells and binds to.
Them.
It is important to highlight that B2 cool is not absorbed, and it turns off the immune response against endogenous type 2 collagen just linking to the immune cells.
After that, immune suppressor cells go out of the payer's patch and reach the joint where they stop collagen destruction.
Thanks to this specific mechanism of action, B2 cool dosage is very low, only 40 mg per day.
Be Too Cool from Bio E Bria, the joint health expert.
The efficacy of Bitucul has been tested in preclinical and clinical studies.
A standard animal model of osteoarthritis was used to evaluate the product.
In this model, osteoarthritis was induced through the intraticular injection of sodium monoiodate acetate that originates cartilage damage.
The study was performed by Manelian colleagues and published and presented in Osteoporosis International Journal in 2015.
In this study, the treatment consisted in increasing doses of collagen that were daily given from day 1 immediately after monoun acetate injection to day 14.
After 14 days, behavioral and biochemical tests to avoid pain and inflammation were performed.
The results showed that the administration of Bol significantly reduced pain at all doses compared to the control group, C bars in blue.
And the efficacy was comparable to those induced by 250 mg per kilo of glucosamine.
See the bar in red.
The improvement in behavioral parameters was associated with the improvement in the biochemical parameters.
B2C significantly reduced interleukin 1 beta plasmatic levels compared to the control group at all tested doses, meaning that was able to reduce inflammation.
Reduction of inflammation was also detected in histologic evaluations in which Bitucul reduced inflammatory infiltrate in joint tissue.
Reduction of inflammation was parallel to a reduction of cartilage collagen degradation, as evidenced by the reduction in the plasmatic levels of C2C, a biomarker of collagen destruction.
In summary, the results described the preclinical efficacy of low doses of Bol as pain reliever by a mechanism involving a protective effect in the cartilage.
The clinical studies results were further supported with the data obtained in two clinical studies conducted with patients with osteoarthritis.
The first clinical study was published in the Journal of Orthopedics and Traumatology in 2008 by Scapelini and colleagues.
This is an observational retrospective one year follow-up clinical study that was performed to elevate the efficacy of Bol when combined with chondroitin sulfate and glucosamine in 100 for patients with osteoarthritis.
The main outcomes included pain determined by base scale, the assessment of the effects of the progression of the disease, determined by the iography using the Kogallon the scale and the measurements of two biomarkers of cartilage catabolism, UCTX1 and UCTX 2.
The results showed that after one year of treatment, pain, UCTX 1 and UCTX2 mean mean values were significantly lower than baseline in both groups.
In particular, as it is shown in the figure, radiological score after one year showed a reduced progression compared to the baseline in the Hanosterittis group after Bitucul in combination with chondroitin sulfate and glucosamine treatment, meaning that patients taking Bitucul reduce structural progression disease compared with the chondral groups.
In addition, the combination of Bitucul, chondroitin, and glucosamine significantly reduce collagen peptide production generated in the progression of the disease compared to the group not supplemented with with Bocul, showing a decrease of the structural progression in hen osteoarthritis.
The results suggest that B2C, in combination with chondroitin and glucosamine, could represent a further protective factor in osteoarthritis, cartilage, by reducing collagen degradation.
The 2nd clinical trial.
Was performed by Baki and and colleagues and published in the Eurasian Journal of Medicine in 2016.
The present study was designed as a randomized single line control trial that was performed to evaluate the efficacy of Bocul in patients with knee osteoarthritis.
39 patients with ne osteoarthritis were included and divided into two groups, one treated with Bool given concomitantly with acetaminophen, and the other with acetaminophen alone.
The efficacy was measured in terms of evolution of pain, measured using the Uele scale, and evolution of joint function using the Womack scale, and quality of life measured using the SF 36 score.
The results show that compared with baseline, the administration of Bituol during 3 months significantly improved joint pain, function, and quality of life.
In addition, comparisons between groups revealed a significant difference in Uveer's walking score in favor of B2C when combined with acetaminophen as compared to acetaminophen alone.
Taken together, the scientific data presented shows that B2C provides negative effect to collagen that, given orally, modulates the immune response at the cartilage level, resulting in clinical improvements and reduction of chain damage.
To sum up, what are the main benefits of P2 cool?
B2 cool by Euderica's native type 2 collagen is a new generation collagen that can help companies innovate in the growing collagen market.
Effective at a very low dose of only 40 mg a day, much lower than doses needed when using hydrolyzed collagen, it meets consumer demand for convenient, low dose products.
And it has been tested in 3 scientific studies, 2 clinical and 1 preclinical, which demonstrates that B2ol supports joint health.
Additionally, Bituco is a product manufactured by Bioria, which has a vertically integrated supply chain providing full traceability and high reliability.
And it is 100% sourced and produced in Europe.
Under a proprietary manufacturing process that ensures the molecule's native form is maintained.
And to finish our presentation, we would like to show you some examples of products containing B2C.
Bul can be found in stand-alone ingredient products such as Aletta from Abbott in Brazil or collagenforte from Vitala in Denmark.
But it is also combined with other ingredients.
Here, there are some examples of different formulations, combining it with hyaluronic acid and bosweia, such as in atrazine from physical in the US with hyaluronic acid only, such as in Coders product in Malaysia, or in a four ingredient formula containing B2C plus glucosamine, chondroitin, and hyaluronic acid, such as in biogenous product in Austria.
Again, we took a low dose, only 40 mg, make it, make it very easy to formulate with other ingredients or alone in a convenient small one a day pill.
That concludes our presentation today.
We would like to thank you very much for your time and now if you have any questions, please feel free to ask.
But now it's time to come to the questions our listeners have sent in during the course of the webinar.
So if I go to the first question.
A listener asked if there, if there, if there are any differences between type 1 and type 2 collagen after hydrolysis.
In, in general, after hydrolysis, there are few differences between types of collagen.
All types of collagen contain repetitions of protein and hydroxyprolene rich the peptides.
Specifically, collagen type 1 and type 2 are fibrile forming collagens, and from a compositional point of view, differences between them are minimal.
One of these differences is the content of hydroxylazine, which is higher in collagen type 2 as compared to collagen type 1.
OK, thank you Daniel for that insight.
The next question I see here is a regulatory one and a listener asked if there are any EU approved claims for collagen.
Actually, there's no approved claim for collagen by the European Food and Safety Agency.
However, consumer knowledge of collagen is so high, 48%, according to FFMG Guru survey, that a product that claims that contains collagen is immediately recognized by consumer as a product with benefits for joint health or other uses.
OK, so in that way you, you cannot put it on the label or that the consumer awareness is already there?
Monica.
Excuse me.
But you can put it on the label, but the consumer awareness is already so high that it's not necessary.
No, what I'm trying to say is that, given that, the consumer knowledge of collagen is so high, once the consumer see that a product contains collagen, he immediately, knows that, this product has a benefit for joint health or other users because they know a lot, about collagen and, and their users.
Of course, OK.
Thank you very much.
Moving on to the, moving on to the next question.
Is hydrolyzed collagen sometimes labeled simply as collagen in in finished products?
Actually, collagen would be the generic name.
And it can refer to both hydrolyzed and native collagen.
Hydrolyzed collagen, collagen peptides, and collagen type 2 are common names used to label hydrolyzed collagen, while native, under-natured, or non-hydrolyzed collagen are the different names used to label native collagen.
OK, I see.
Thank you for the clarification.
But what would the differences between hydrolyzed collagen and native type 2 collagen regarding the efficacy for joint health be?
Yes, in terms of efficacy differences are derived from the different mechanism of action.
So hydrolyzed collagen is a source of a specific amino acids such as proline and hydroxyproline that play play a role in maintenance of connective tissue like articular cartilage, so it has a protective effect.
On the other hand, native type 2choin has an immune-mediated mechanism of action that reduce cartilage inflammation and consequently induce clinical improvements.
Oh, very, very detailed.
Thank you, Daniel.
And on the functionality of the, the ingredient you're talking about in the slideshow, one of the listeners asks how long B2 cool should be taken for.
Yes, according to the studies, it is recommended to take the product for at least 3 months.
OK, and also building On this similar topic, another listener asked that if if it's necessary to take Bol on an empty stomach.
Yes, taking 80 mg once daily on an empty stomach guarantees that the native type 2 collagen interacts with intestinal cells and elicits its effect.
So any changes in these conditions could potentially interfere with the efficacy of the product.
OK.
And then is it also necessary to take 40 mg once a day, or can it be split to 20 twice a day?
So, according to, to our knowledge, it's with 40 mg per day is when we could guarantee that the product has elicit the the full effects.
OK, I see.
Thanks for the clarification.
And another question that's just come in, it's asking if there's any data on the efficacy of B2C4RA.
No, no, no, we don't have any specific study evaluation, evaluating the efficacy of Bol in patients with this specific condition.
OK.
Thank you for sharing that.
And one more question is can hydrolyzed collagen and native type 2 collagen be combined in one product?
Yes, yes, yes, they could be combined in one product because their mechanism of action are fully compatible.
OK, so that gives there's some scope there for future MPD perhaps.
Thank you.
It's really interesting.
Actually, we've run through our questions for today, from the webinar.
So thank you all of our listeners for sending them in.
I'd also like to make the point that any unanswered questions that have been submitted, they will be responded to via email, by our experts.
And also now that our webinar has come to a close, I'd like to draw your attention to the 3 questions which will appear after the webinar is finished.
Bayo Vic, I'd really appreciate, if you could take an extra minute to complete the small survey for some further information.
And one last note from me is that to keep up with industry news, please visit food ingredientsfirst.com and nutritioninsight.com and sign up to our newsletters.
Thank you very much.

















