What New Research Says About Cartilage Regeneration and Joint Longevity

What if a human trial of over 1200 patients showed improved mobility and reduced pain in osteoarthritis (OA) patients using a natural combination of boswellia and celery seed extract? What if a second follow-up randomized, placebo-controlled human trial found that within 90 days, this same combination increased OA patients’ ability to perform a walk test by over 50%, reduced markers of cartilage degeneration by half and increased markers of cartilage regeneration by half. This is what the research team at Calroy Health Sciences have discovered, putting a tremendous amount of work and financing into studying the effects of the uniquely developed Cartigenix-HP. Not only that, increased joint space at the end of the trial was clearly visible via radiography, and 90% of the intervention group did not need any “rescue” pharmaceutical medication at the end of the 90 day period (compared with only 20% of the placebo group) and this effect was sustained beyond the end of the trial. I have to say, I am impressed and excited about the potential for this new product to help my patients and I am thinking about other applications like OA prevention and osteoporosis! Listen in to find out more.  ~ DrKF

Osteoarthritis isn’t just a wear-and-tear joint issue—it’s a systemic inflammatory condition often rooted in gut dysfunction. In this episode of New Frontiers in Functional Medicine, Dr. Kara Fitzgerald talks with microbiologist and Calroy Health Sciences advisor Kiran Krishnan about how chronic low-grade inflammation, also known as inflammaging, accelerates joint degeneration and contributes to cardiovascular disease.

Kiran introduces Cartigenix, a new supplement featuring clinically studied extracts of celery seed and Boswellia, shown to regenerate cartilage, reduce joint pain, and improve mobility—without the side effects of NSAIDs. You’ll also learn about the critical role of the gut-joint axis, why liver function matters for effective joint repair, and how preventative strategies can support healthy aging and long-term mobility.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald: Hi everybody, welcome to a new Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine, and of course today is no exception. If you’re with me on YouTube, you can see I’m sitting next to the very highly regarded Kiran Krishnan. He is actually a long time colleague. We met back at CHS in 2021, I believe, and I’ve been an admirer of his career ever since. Let me read his bio to you and then we will jump into this interesting conversation. Kiran is a research microbiologist and a health and wellness expert who aims to make complex information understandable to all. He has founded a number of successful health companies and supplement companies over the last 20 years, including co-founding and leading Microbiome Labs– I think that’s where a lot of us know who you are from– And this is a preeminent microbiome therapeutics focused brand among healthcare professionals.

Dr. Kara Fitzgerald: He’s currently co-founder and partner in three other companies and aims to revolutionize wellness care. Well, you actually have made a really big inroads into that. He’s conducted and published several research studies in journals, has published chapters in scientific textbooks and reference books. He’s got global patents and he’s a sought after speaker on human health and the microbiome. Kiran, welcome to New Frontiers.

Kiran Krishnan: It’s a pleasure to be here. Thank you so much for having me. It’s my first time here, so I’m excited.

Dr. Kara Fitzgerald: Awesome. I had such a great time getting to know you way back when and have kind of paid attention to your career because it’s been really quite extraordinary. I mean, you are a key player and really helping to bring what we’re doing in functional medicine forward into the world. But here you are and we’re going to be talking about a new Calroy product, which I’m quite excited about, Cartigenix HP. And when I was talking to Calroy about doing this podcast with you, and actually about your involvement in the development of this product, I was surprised because I firmly associate you with microbiome therapeutics. And so just give me a little bit of the backstory on how you became interested in this and maybe why it’s so important.

Kiran Krishnan: Yeah, so when I think about the things that really move me in terms of getting excited, interested, devoting a lot of time and effort into, typically they’re megalomaniacal things, right? I’m always thinking about really big problems. My interest in getting into the world of the microbiome was to try to solve what I thought were the biggest problems with gut health and I think most people would agree, that one of the biggest problems with gut health was leaky gut or endotoxemia as it is well described in literature. So we founded Microbiome Labs, and developed a completely new type of probiotic to address endotoxemia. And in fact, the first paper we ever published was on endotoxemia as a frontier paper in a well-known gastroenterology journal. And it’s that kind of thinking that kind of led us to looking at solutions for things like osteoarthritis. The connection here is an underlying obsession around chronic low-grade inflammation. And when I started really looking into the problem of metabolic endotoxemia, and some of this stemmed from a 2015 publication in Frontiers of Humanology. It was a meta-analysis paper that basically concluded that the number one cause of mortality and morbidity worldwide was stress-induced endotoxemia.

Kiran Krishnan: And that was a little bit mind-boggling to me because there’s lots of things out there that kill people. And the fact that these authors, if you will, had the audacity to boil everything down to this one ground zero of health dysfunction, which is the lining of the gut and the resulting pathologies, it became incredibly intriguing to me to really dive into that and understand that process. And at the root of that process is the resulting chronic low-grade inflammation. And so I became obsessed about this idea of resolving permeability in the gut and then also understanding where else chronic low-grade inflammation plays in the body. And there’s lots of places, right, of course, in the brain, on the skin, in joints, and so on, and one of those areas is in conditions like osteoarthritis. And the reason why I then became really interested in osteoarthritis, specifically, as a byproduct of chronic low-grade inflammation is because the development of osteoarthritis will then parlay itself into much more serious problems, right?

Kiran Krishnan: Because as your joint degenerates, you’re not only then, of course, experiencing pain and inflammation and the quality of life disruptions where then people are taking medications like NSAIDs every single day, or opioids, or any number of pain medications to manage it, they also start to become immobile. And the lack of mobility leads to things like sarcopenia and metabolic syndrome that then lead to a big cascade of much more serious conditions, right? Diabetes, Alzheimer’s, heart disease, and so on. And all of that disrupts the microbiome even further. And so, just connecting the dots simply, to me, it was a matter of, okay, we have a solution for the lining of the gut, and if there’s more solutions to the lining of the gut, let’s bring it on, let’s do that, right? That stops a big source of chronic low-grade inflammation.

Kiran Krishnan: But then when we look at a foundational issue like joint degeneration, which becomes a stepping stone to more complex chronic conditions, can we resolve that problem, and in a way that actually goes after the root cause and creates change that goes beyond masking the problem, which is what pain medications do. Right? So that’s how we got connected with it. And then after I sold Microbiome Labs in 2021, I really started to look at herbal medicine because I felt like there was a big change that was needed to happen in a lot of herbal medicine verticals. In particular, better identification and better traceability of the herbs. And then number two, more original research around what the herbs are, what they do, what the active ingredients are, and so on. So that’s also another way in which we ended up parlaying into the actives that are found in Cartigenix.

Dr. Kara Fitzgerald:That’s a really interesting story. Wow. So tackling just the foundational problems, we could go on about, you know, the issues from joint health origin, linking to significant secondary fallout, and then tying that back into the gut. That’s really…

Kiran Krishnan: Well, and sorry, one more thing to interject there. Another area that I get really passionate about, because I’m such a fan and consummate supporter of functional medicine, holistic health, right? My lifetime career goal is about providing functional medicine, holistic health practitioners, with the tools they can use to effectuate health and wellness in their patients, especially where allopathic medicine completely fails. And allopathic medicine ends up doing things that are maybe masking the problem or just kicking the can down the road in some way, and then the patients come to holistic health and they don’t necessarily have a really great solution yet. That also becomes a big passion of mine.

Kiran Krishnan: That’s in part why Microbiome Labs existed as well because when I first was looking at the probiotic offerings back then, I felt like there was a significant gap in the therapeutic regimen. Our probiotic therapeutics were not complete and dealing with leaky gut was not complete. So in this case, I just put myself in the shoes of a joint health patient and I’ve been dealing with degeneration of the joint and pain and discomfort and all that and at my allopathic doctor I’m basically getting recommendations for NSAIDs and maybe it’s going to prescription pain medications. That’s not really a solution. My condition is getting worse and worse over time. And then if I went to a holistic health practitioner, there may be some other things they would try, but they also didn’t have a slam dunk product that you can provide me that would alleviate my issue, right? So that’s another thing too, empowering and providing tools to holistic and functional medicine practitioners.

Dr. Kara Fitzgerald: And obviously, that’s not to discount the power of the gut work that you have done– some really incredible work around the power of transforming the diet and cleaning up nutritional insufficiencies, et cetera, et cetera. So all of that, I think, is an essential component to this but I think you’re right around there being some limitations in our therapeutics. And before we talk specifically about what the product is, I want to just give you a shout out, and also Calroy, around my gratitude to elevating the conversation in functional medicine. I mean, on my platform, we participate in conversations with those people who are willing to commit their time, their effort, their financial investment, because research is incredibly expensive, to really identifying the correct ingredients and identifying that they work, that they work in humans, at what doses and it’s just… It’s an exciting time to be in this medicine. It’s a really exciting time because there’s an elevation that starting to happen and so thank you for being a part of raising the bar because ultimately that serves those of us treating and our patients.

Kiran Krishnan: Yes. Absolutely. Yeah. And that was the start of Microbiome Labs. It’s like, can we create a new standard for what it means to develop a probiotic product? The level of research you should have, the level of identification and scrutiny on the strains and what their impact is on the microbiome itself. And then all of that goes along with the development of the Cartigenix product, and when we talk about the research that we have, it is second to none in terms of joint health support, inflammatory support. And it was such a great fit with Calroy because Calroy already had a precedence of having very well researched products, very well understood products, right?

Dr. Kara Fitzgerald: Yeah, a high bar.

Kiran Krishnan: So that really high bar. And there’s not a lot of companies that fit that formation so it became a really a natural fit to partner with Calroy on this.

Dr. Kara Fitzgerald: That’s cool. Well, I appreciate all of the backstory because people are wondering how you ended up partnering on this product specifically. So that makes a lot of sense. All right. So we want to talk about the ingredients in this product. And then I think you laid out the problem, you know, this low-grade systemic inflammation that’s happening, really in all of us. I mean, we can think about inflammaging, just as we age. We’re all dealing with some of this and clinically, one of the first places we all see it show up is in painful joints. And you know, on an x-ray, like I just had a thumb injury. I crashed recently out in the desert here in Mexico and they identified some mild osteoarthritis and it’s an acute inflammatory condition.

Dr. Kara Fitzgerald: But of course, if you take images of any of my joints these days, we’re going to see some deterioration occurring and, you know, that’s kind of de rigueur on the journey of getting older. And with that, I think nobody escapes the fact that there’s going to be some discomfort. So we want a product that’s going to help with that, that’s going to be impactful on the pain, but it seems like there’s some cool research actually suggesting that there may be some reparation happening with Cartigenix. It might be turning around. So talk about what it is, how it works, and some of the science on it.

Kiran Krishnan: Yeah, and what you said is completely true. With age, we’re going to get some degeneration of joints, cartilage, things like that. Same thing that happens in osteoporosis, over a net period of time as you age, you’re going to be losing bone more so than you can rebuild it. But one of the hallmarks of healthy aging and maintaining functionality is going to be a continuous push back in the balance of degeneration versus regeneration. Where these conditions really accelerate is when the degeneration far outpace any capability to regenerate. That’s really the hallmark of aging.

Kiran Krishnan: If you consider something like the mitochondrial free radical theory of aging, the whole mechanism around that is that the mitochondria of cells start to degenerate faster than they can rebuild. And over time, what happens is you get a predominance of dysfunctional mitochondria so the cell doesn’t function the way it’s supposed to, and as a result, the tissue that the cell makes up doesn’t function the way it’s supposed to. So we want to bring a lot of that back and bring back some balance to it. And so herbs do amazing things, as everyone knows who’s listening to this. For us, it’s a matter of modernizing some of that understanding and then taking deeper advantage of the amazing chemistry that’s within herbs.

Kiran Krishnan: So we started our investigation in two ways. The first one— So there’s two ingredients in Cartigenix. One is the celery seed extract and the other is a Boswellia extract. And everybody listening to this has heard of celery seed and heard of Boswellia and probably use versions of it in practice in one way the other. But I can assure you these are very, very different and we’ll talk about how we came about a very different way. So let me take you back a little bit on the celery. The celery is an interesting story because in a previous, previous company to Microbiome Labs, I had a partnership with a group in India who are working right now on these ingredients. That group in India was originally called Beagle International and I had a company called New Science Trading and Procter & Gamble was looking at developing— This was in 1999, and I was a full grown working adult then, so that ages me to people to understand how long I’ve been around with this stuff.

Kiran Krishnan: In 1999, Procter & Gamble was working on a project to develop a natural anti-pain, anti-inflammatory compound– so COX and LOX inhibitors– and they were doing it for large breed dogs and animals that suffered a lot of osteoarthritis and arthritic issues, hip dysplasias and so on. So they started investigating a lot of different herbal compounds and there was some indication that celery seed had some of these functionalities, but the problem is with the types of celery seed that are most commonly found, the extracts don’t have the right hydrocarbon profile to provide COX and LOX inhibition, because most of them are phthalates and they will have a 3nB conformation. The 3nB versions tend to be very strong antioxidants and great for neurological health and a number of things, but they don’t provide COX and LOX inhibition.

Kiran Krishnan: So then this research group with Procter & Gamble did a global search of all kinds of different types of celery and they found that one genus and species of celery that’s grown in the northern part of India had the right hydrocarbon profile where it had the right compounds and it could act as an allosteric inhibitor of arachidonic acid. So for the practitioners that are listening, if you remember your biochemistry, arachidonic acid is the is a primary compound that differentiates into lipoxygenase and cyclooxygenase, and that’s where you get all your pain and inflammation signals from.

Kiran Krishnan: And so anytime you have an allosteric inhibitor of arachidonic acid, you don’t differentiate into COX and LOX and so you can reduce pain and inflammation that way. So they found this unique celery and then they had to go into process development so they partnered with an Indian group called Beagle International to develop that product in India. Now, this is a little bit of a tragedy, but fortunately the work continued, but the office in Procter & Gamble that was managing this project was in one of the World Trade Centers.

Dr. Kara Fitzgerald: Oh geez.

Kiran Krishnan: So of course we all know then what happened in 2001, so that project got shut down within Procter & Gamble, but our group in India had already worked on it for a couple of years and had made significant progress, including doing a number of animal studies showing real significant reduction in pain and inflammation. And so once that was shut down within P & G, our group went to P & G and said, hey, we want to buy out all the intellectual rights on this. P & G said, no problem, we are no longer pursuing this, and so our group in India had it and I had started working with them back then. They went on to develop it then as a human product instead of an animal product because of the issue of managing pain and inflammation in a healthy way. And then it became a massive product in India where it actually became a prescription pain medication, and then it became a product in Korea and Australia, most of it under medical foods or even some prescription level regulatory status. So that is the history of the celery seed.

Dr. Kara Fitzgerald: Wow. Wow.

Kiran Krishnan: So now since then, we’ve done a number of studies, more developments, refined it more, did better identification, have better fingerprinting, extraction process, and so on. The Boswellia is a little bit different. The Boswellia, we actually got hired by a company a number of years ago to look at Boswellia in a different light because Boswellia has about eight or nine actives that are very well known. Most of them are in the family of Boswellic acids called AKBAs, and those Boswellic acids are known to have anti-inflammatory properties, so we started investigating Boswellia. We brought in seven analytical chemists who worked on different areas of the project to try to understand what other compounds are present in this amazing plant.

Kiran Krishnan: And so they started pulling it apart, extracting it. They worked on it for about five or six years and eventually what we found out is we identified two other active ingredients within the same absorption spectrum and the main one called serratol. That serratol, not only does it also have anti-inflammatory effects like the Boswellic acids, but it has tissue repair function, right? So then we said, wow, okay, we have to develop a process to standardize the serratol and so we developed our own proprietary process to standardize the serratol, standardize the celery seed, create a synergistic combination and that’s where the combination of ingredients came from. So combined, it’s actually, starting in 1999, between the two ingredients, probably 35 years worth of work combined into this, right? To create this product that has these two synergistic blends that do things that no other natural prescription on the market can do in terms of repairing and rescuing joints. So it’s very exciting to be able to bring this to market.

Dr. Kara Fitzgerald: It’s extraordinary, the story that you’re unfolding here. It’s extraordinary. I did not, of course, know that celery seed had the potential to inhibit COX and LOX to that extent. I, of course, know about Boswellia as I think many of us do. It’s known for its ability to inhibit LOX activity. And all of those downstream compounds produced in the arachidonic acid cascade, those are the first step in any inflammatory pathway, just across the board, whatever flavor, from anaphylaxis to inflammaging. And so obviously, I’m thinking about other indications for this but I’ll put a pin in it and maybe we can circle back to that later.

Dr. Kara Fitzgerald: What do I want to ask about? I’ve got a ton of questions around dosage and duration and degree of inhibition, all of that. But I just want to get to the serratol bit, how you figured out that it engaged in tissue regeneration. Did you have a suspicion that such a compound would exist or were you just like, let’s explore the other bioactives here and see what they do. And maybe you started with with cell studies and then to animal studies and you began to see that. And any mechanistic information I’d be curious about. And then let’s talk about how you identified therapeutic dosage. I would imagine this works pretty darn quickly as well. So let’s start with what I’m throwing out.

Kiran Krishnan: Yeah, and I can give you the overall results from the two clinical trials as well, which is really quite profound. And then there’s a really interesting inadvertent result from the clinical trial that I think is really interesting to speak about. But one of the things that we’ve become quite good at is doing something called in silico trials. For anyone who’s not familiar with in silico trials, they’re really trials in the computer using AI to help you identify potential mechanisms of action based on understanding the compounds. And there’s two components, there’s a serratol component and another chemical component that’s also unique that goes along with serratol. So there’s really two molecules here that are unique. What we were able to do with our analytical chemists, is be able to discern the full molecular structure and three-dimensional structure of these two molecules. So that’s step one.

Kiran Krishnan: Once you understand the full three-dimensional and molecular structure of these compounds, what you can do is you can put it into an AI, and you can ask the AI to search all known receptor sites, pathways, and everything that’s available in the public domain to see where these types of compounds may function. And what we saw was that the AI had predicted that there may be a function in tissue regeneration, especially in mucosal or connective tissue, and in part by inhibiting degeneration of the tissue, by inhibiting things like matrix metalloproteinases, and then upregulating some transport proteins that bring reparative compounds back to the tissue.

Kiran Krishnan: And some of these transport proteins, or sorry, transport channels, they are proteins as well, can get inhibited by age and inflammation. This is part of why repair becomes really difficult, right? So we said, okay, so there may be a reparative quality to this component of Boswellia, so we now have Boswellia that we know has anti-inflammatory properties because of all the known boswellic acids and all that, but then we may also have reparative quality. So then the first study we did to figure out if we’re actually repairing anything was a gastroprotective study. And the reason we did that is because we said that is very relevant to anyone that has joint issues because people with joint issues have been on NSAIDs for years and they have lots of ulcers and degeneration of the gastric mucosa.

Kiran Krishnan: So we said, okay, if this thing can regenerate connective tissue, mucosal tissue, when we use it, we should be able to stop the degeneration of gastric mucosa and reverse it. And there’s a very well-known model of studying gastric protectiveness or regeneration and so we did that study and what we found was that this was very gastroprotective. It inhibited the formation of ulcers and it recovered and reduced ulcer index and ulcer severity compared to the positive control where you use a compound to induce ulcers in this model. We actually recovered the system better than the positive control that is a known recoverer of the gastric ulcer index. So right away, we’re like, oh my God, this thing can actually regenerate tissue.

Kiran Krishnan: Now, that didn’t necessarily mean that we would regenerate tissue in the joint, right? So then we had to go to clinical trials for that. The first clinical trial we did was a very large scale trial, a 1,268 patient trial. Nobody in the supplement industry does 1,200 patient trials, right? But we wanted to do it because we had the opportunity to pair with a hospital to get this done and we really wanted to see, in a population basis, are we going to improve pain and inflammation, and improve mobility, and reduce WOMAC scores. WOMAC is the criteria for actually measuring osteoarthritis severity, which looks at pain, stiffness, mobility, and so on. So we said at a population level, if we can reduce pain and inflammation, then we know we have something here, and then we want to go deeper beyond that.

Kiran Krishnan: The first study completed and published, I think, in 2021 and we saw very significant reduction in pain, inflammation, improvement in mobility, improvement in quality of life across the board, compared to placebo. So that in itself is exciting. Then the next study, we said we want to do the same thing, smaller number of people, 60, because we really want to get into the mechanisms of action and we want to see what’s happening with the joint itself. So when we want to look at what’s happening with the joint itself, there’s a few different ways to do that and we did all of them.

Kiran Krishnan: The first way is radiographs, so we actually did radiological pictures and measurements of the actual joint, because what you see in osteoarthritis is a loss of that space between the two bones and then you start getting bone on bone rubbing. You can also see synovial fluid inflammation and then soft tissue degeneration and then the bone that attaches to the cartilage, that bone starts to degrade as well. So you can visualize all that on the radiographs and then you can measure all that through biomarkers as well. So the exciting result that we got from this study was we repeated all of the WOMAC and the VAS pain scores from the big study that we did and there was significant reduction starting at seven days. You start to see a significant decline in pain, significant decline in inflammation, and a significant increase in six-minute walk tests. To me, that’s like where the rubber hits the road. That’s your ability to walk down the driveway to go get the mail. We increase the amount of distance they can cover in a six-minute walk test by 57%, and so we start seeing improvements there.

Kiran Krishnan: But the two areas that we saw that were really exciting was we saw around a 50% reduction in all of the markers of cartilage degeneration. So we’re stopping the degeneration. There are well-known markers for this, UCTX and CTX, and then we started to see a 50-ish percent increase in cartilage regeneration markers. So now we’re seeing biochemical evidence that we are rebuilding the joint beyond stopping the pain and inflammation. And then we start looking at the radiographs and we go, wow, you look at the before and after radiographs, no or very little space between the knee joints and then all of sudden, boom, it looks like they’re 25 years old again. The space has returned. And then where all that really gets memorialized for us is in this part of the study. This is the inadvertent part that I mentioned.

Kiran Krishnan: In this part of the study, it was really exciting because any ethical committee— Because you’re doing study on a population like osteoarthritis patients and they’re not supposed to be on medication as part of the inclusion criteria— We had to give them rescue medication when they came in for their visits if they complained of too much joint discomfort and the rescue medication was celecoxib, which is a prescription pain med. And so by the end of the 90-day part of the study, 80% of the placebo group— and of course we didn’t know this during the study, it was blinded— but after you unblinded it 80% of the placebo group was back on celecoxib. Most of them, more than half of them, came back on at day 45. So halfway through the trial half of the placebo group was back on prescription pain meds. Only 10%, even at the very end of the trial on the treatment group, was on celecoxib. So 90% of the people in the treatment group did not need to come back on rescue medication.

Kiran Krishnan: And here’s the crazy thing, all the rest of the data where we compared WOMAC pain scores and mobility and inflammation and all that, most of the people in the placebo group were on rescue medication at that point. So when we unblinded the data and we’re comparing treatment to placebo, what we’re actually comparing is treatment to prescription pain meds and we still did significantly better than the prescription pain med group. And then once the study was ended in 90 days, people stopped, whether taking the placebo or the the Cartigenix, and then we followed them for another 30 days to day 120, and then up to day 120, just one other person on the treatment group went on celecoxib. So still 87% of the treatment group never went on rescue medication and 100% of the people in the placebo group by now were back on their medication, right?

Kiran Krishnan: And the radiographs tell us why this is, right? The radiographs tell us why is it that people did not go back on their rescue medication in the treatment group. It’s because we’ve actually rebuilt their joints. You see it in the radiographs. Their spaces are back, the cartilage is back, they are mobile again. They don’t have pain. They don’t have inflammation. So it’s a super exciting thing to see in a natural product clinical trial, because what we’re seeing here is just the amazing power of nature to provide us with these critical compounds that just rebuild our system.

Dr. Kara Fitzgerald: It’s extraordinary.

Kiran Krishnan: And it’s just extraordinary because it’s all here already. We don’t have to invent any of it. We just have to be smart enough to look for it in the right places and then test it. So that’s why this particular product really services all of the things that I get most passionate about. And so it’s really exciting to be able to bring it to market.

Dr. Kara Fitzgerald: Yeah. It’s tremendously cool. It’s extraordinarily badass. When Andy from Calroy started to talk about it, I can see why everybody was so jazzed up about it and was really looking forward to us having this conversation. It’s extraordinary. By the way, everybody, we will link to those papers and of course, we’ll link to Calroy so you can go and learn more about it and check out the products. You know, I was sort of curious when you were talking, in the traditional use history of Boswellia, was there anything known about it being regenerative? Was that in any… You know, you’ll be able to walk like a kid again? Or was it only thought as pain relief? It’s just sort of an aside. I’m curious if you have any knowledge on that.

Kiran Krishnan: Yeah, so even in the world of Ayurveda, it’s really known as an anti-inflammatory. There is some recorded history of use for improving bowel function, and that may be some of the gastroprotective side notes that you might get out of it, but generally it’s known as an anti-inflammatory. And I think in the supplement world, it’s purely anti-inflammatory because no other Boswellia standardizes it to the serratol. You won’t find the serratol component and then the other compound that goes along with serratol, you won’t find those two in any of the other Boswellias in the market. You’ll find all the Boswellic acids and all that are good anti-inflammatories, but you won’t find the serratol component.

Kiran Krishnan: So that’s where we’ve kind of accelerated past what is known about Boswellia and then that’s also part of the basis of our global patents that we filed on this is because we now have a unique identity for Boswellia. We have a unique identity for celery. And what we’re showing is that there’s a actually a unique synergy between the two. There’s no competitive mechanisms at all, which is really interesting because even though celery has anti-inflammatory and Boswellia has anti-inflammatory, they both actually approach the anti-inflammatory mechanisms from different pathways. Boswellia does so from the immunological side. It reduces the overt expression of TNF-α and all that from dendritic cells and natural killer cells and so on that end up getting involved in the inflammatory cascade. And then we know celery does the arachidonic acid inhibition.

Kiran Krishnan: So we’ve got two very different mechanisms that we go after inflammation. And then you brought up a really interesting point, and I love your clinician mind, is the other applications for this. At the end of the day, the other thing that really got me excited about this is when you look at the serum inflammatory markers in these individuals, all of them are coming down so significantly. We’re talking about TNF-α, IL-6, right? IL-12 beta, IL-1α, like the quintessential markers that are associated with Alzheimer’s, heart disease, diabetes, autoimmune conditions, virtually everything. All of those are coming down. Right? So there is a global support.

Dr. Kara Fitzgerald: Well, and CTX (C-terminal telopeptide) too. CTX is crazy. This is a marker that we routinely order when we’re tracking our osteoporosis patients. We have not thought about it with regard to looking at our osteoarthritis patients and whether we’re turning things around. So that’s really extraordinary that you looked at it for that. And obviously it’s another indication potentially for the product.

Kiran Krishnan: Yeah, and one of the reasons why that became so important in the joint space is because the bone that the cartilage actually attaches to, starts to degenerate really fast when you get cartilage degeneration. And so you actually get osteoporosis within the joints along with the osteoarthritis, so that’s where the osteo component comes from, I think to a certain degree, in the naming of it, because there is bone degeneration as well in that space. And so the CTX became really important and the fact that we can improve that by 50% is really amazing, right? It’s amazing.

Dr. Kara Fitzgerald: It’s nuts. As soon as you said that, numbers flashed by because I do use CTX so routinely on certain patients who’ve got really markedly elevated levels that we need to work with.

Kiran Krishnan: Yeah. Well, and then the other one is matrix metalloproteinases. So MMPs, right? MMPs are functioning all over the body, doing all kinds of wreaking havoc in many places if they’re overly expressed, right? There’s all kinds of weird remodeling happening in the body and we brought that down quite significantly. And again, that’s at the serum level. We did investigation in some of the synovial fluid and we see the inflammation, all that going down in the synovial fluid.

Dr. Kara Fitzgerald: Really?

Kiran Krishnan: Yeah. But in addition to that, it’s the serum stuff that’s super exciting to me. And then I’m just imagining— And I’m a very visual thinker, right? And so I’m always daydreaming and imagining things in my head and so then I’m just imagining the results of this and with a patient that’s now walking again and having reestablished mobility and improving their metabolic health as a result of that and all that. But then their overall inflammatory picture is going down as they’re starting to get up and move and walk and do exercise. To me, that’s just such a wonderful thought to think about being able to do that for 50 million people. The statistics show that it’s upwards of 53 million adults that suffer from this and so it’s mind-boggling, right? The core morbidities that go along with it and all that. So I’m very excited that functional medicine practitioners, holistic practitioners, will have a powerful tool to restore these patients with Cartigenix

Dr. Kara Fitzgerald: Yeah, I’m excited to launch it in practice. Actually, I’m just excited to try it, to be honest with you. What else do I want to say around it? I think the other important thing I want to just underline is that you found the right species to use, especially for the celery seed. And then with Boswellia, the right elements, you know, a new bioactive not really characterized before your research. So that’s awesome. And just figuring out how to dose it. Clearly you lighted upon the therapeutic intervention that’s going to work and in your study, people stopped it, you still saw benefit, you said thirty days out I believe, right?

Kiran Krishnan: Yep. No washout in 30 days. Yeah.

Dr. Kara Fitzgerald: And so dosing, you’ve lighted upon the appropriate dosing and it’s manageable. I’m curious what it is. And then also, when we’re prescribing in practice, is this something that we’re going to be using continually? I mean, what about just for prevention? I mean, if I get a total body x-ray, we’re going to be seeing some elements of deterioration, as I’ve already identified in my thumb. I mean, this seems to be an essential preventative component and we’re going to be capturing inflammation. I mean, IL-6 is CRP, basically. Anyway, there’s lots of places we can go with that. But speak to those bits I’ve just thrown out at you.

Kiran Krishnan: Yeah, those are really important. So, and we looked at HS-CRP too, and that comes down quite a bit, which is great. So the dosing, we do use some of the in silico modeling to help guide us towards a dose and based on that, we actually did two dosing studies. We did one at what is the full dose, which is 1,100mg per day. So 550mg BID. The Cartigenix product is basically two caps a day so you can take one cap BID. If that’s inconvenient, you can actually take them both at the same time and that’s fine.

Dr. Kara Fitzgerald: Oh, you can. Good.

Kiran Krishnan: (Yeah, we’ve done the pharmacokinetics and it stays active in the blood and serum for most of the 24-hour periods so you’re good taking it once a day as well. And then here’s what we discovered in the dosing study. We have a half dose study coming out, which is just 550mg and we have the 1,100mg. The 1,100mg, of course, provided the most benefit for osteoarthritic joint patients in terms of rebuilding the joint and all that. That’s the recommendation for people who have frank joint issues. But for the rest of us that are just aging, we’re getting older, we’re still active, we’re healthy, but things hurt, right? And as we get more active, as we get older, things will hurt even more. And like you said, all of us have some degree of degeneration of joint and soft tissue and so on and all of us are trying to manage inflammation.

Kiran Krishnan: So the half-dose study actually showed a really potent anti-inflammatory, anti-pain effect and modulation of things like CTX, but at a reduced level than the full dose. So there is a dose dependency. So for someone like me, you know, I’m 48 years old, I’m fairly active, I still do a lot of things, cycling long distances and things like that, I don’t have any frank joint issues, but I do have aches and pains, and I’m always trying to bring down inflammation. So I take once a day, every day, as protection.

Dr. Kara Fitzgerald: You take 550 or are you taking the 1100?

Kiran Krishnan: I end up taking 550 most of the time. I’ve actually went through two months of taking 1,100mg because I started a whole new kind of workout. I started a lot more kettlebell stuff and swinging things and all that, right?

Dr. Kara Fitzgerald: Me too, yeah, yeah.

Kiran Krishnan: Yeah. And that stuff can hurt, right? And my hips, you know, historically have always been tight and kind of inflamed from all the cycling. I used to be a competitive cyclist, so I spent hours on end on the bike racing and so I get a lot of tightness around the hips and lower back and stuff. And so when I started doing a lot of the kettlebell work and all that, went to 1,100mg a day and that helped a tremendous amount. And then now, as the season gets on with having more warmer days, I’ll start cycling more, so I’m doing less of the really aggressive kettlebelling and all that, so then I’m back on the 550. So my recommendation, because inflammation is something that we all want to curb and it’s hard to find something that brings down inflammation as much as this product does, that I would say that at least 550 should be a maintenance dose for most people if you’re over the age of 35. And then if you have any sort of joint issues at all, 1,100. That’s where people should be.

Dr. Kara Fitzgerald: That makes a ton of sense and you’re slowing down deterioration, I think, at either dose. But what about pain? You reported in the study that it was seven days before there was just a significant change happening, but mechanistically it seems to me that probably you would experience something sooner. So I’m curious about that and maybe your own anecdotal experience.

Kiran Krishnan: Yeah, so in our empirical look at this, most people will feel an effect in the first three days. Now, in the studies, it’s always seven because that’s always the first visit. The first visit is a week into starting. We don’t check with them prior to the first visit, so many of them may have felt improvement in the first two or three days, but I would say it’s noticeable, especially if pain is an issue for you, it’s noticeable in three days or so. Part of the reason why it may even take three days and it doesn’t work like an NSAID, for example, in 12 hours is because the pain reduction kind of goes along with the inflammatory reduction as well. And we know that it takes the body a little bit of time to simmer down from inflammation. Especially when there’s an ongoing input for inflammation.

Kiran Krishnan: And so we’re seeing that it takes a little bit of time for the inflammation to go down and then for the COX inhibition to take effect— And the COX inhibition is different than the COX inhibition with NSAIDs, which also then disrupts the gut, right? So I think it’s because of that, because we’re going after true root cause pathways, that need to be modulated that mimic healthy function, it takes a few days, but most people feel something in like the third or fourth day. And I don’t want to skirt over the idea that our first study on this was on gastroprotectiveness, right? So think about your patients that have been dealing with H. pylori and reflux and gastritis, right? Any sort of gastritis, they’re eating away at the gastric mucosa and we’ve shown that we can repair the gastric mucosa with this. So even there is another auxiliary benefit.

Dr. Kara Fitzgerald: Yeah. It’s so interesting. Extraordinary. I mean, anybody who’s taking a non-steroidal anti-inflammatory is going to be sort of propagating the mechanisms that drives the inflammatory condition they’re trying to shut down and so it’s awesome that this does not. It’s does the exact opposite. Okay, so I’ve got a handful of questions. Now, clearly I know folks are thinking as I am, this was a stand-alone intervention, so you weren’t changing diet, you weren’t prescribing collagen and you weren’t doing all of the other things that we would be doing in functional medicine. What’s your anticipation if they’re still doing whatever dietary pattern they came in with, which could have been who knows… You know, it could have been a fast food dietary pattern. They could be undiagnosed celiac consuming gluten. I mean, it could be, right?

Kiran Krishnan: Yes.

Dr. Kara Fitzgerald: I mean, with these additional functional medicine components, like we would want to be using some collagen or maybe we’re boosting protein, et cetera, and helping with digestion, what are your thoughts? It seems to me that we could see something powerful in concert with a full functional approach.

Kiran Krishnan: Yeah, I think a couple of things. I think number one, the effects that would be realized upwards of 50% faster and I think that’s evident in our empirical evidence. So for example, when I’ve given it to people who are not super health conscious, but they’re like, I have a pain thing. What’s that joint thing you’ve been working on? I give it to them and they feel an improvement three, four days, and they notice it, and then it just gets better and better steadily. But then when it’s people I know that are really health conscious and fit and are within our world, their impact is much faster. Not to call out Andy, but Andy at Calroy had some faster impact as well, right? She had an issue, I think on her hand or one of her joints, and I think she felt it within the first couple of days in a much more profound way.

Dr. Kara Fitzgerald: Wow.

Kiran Krishnan: So I think everything would get accelerated by 50% and I think the joint repair would get accelerated as well. And my hypothesis would be that the dose that we have will actually be utilized much more widely throughout the body. So I think you’ll start to seen a bigger impact on more joints throughout the body versus just the bigger joints like the knees and so on. And that’s the exciting part for me of getting this in the hands of holistic and functional medicine practitioners and then starting to get the feedback from them because we saw the same thing with with MegaSporeBiotic right? So with Megaspore, our first endotoxemia study we did was in college students who were not doing anything healthy for themselves during that period and yet we saw this profound reduction in leaky gut, endotoxemia, inflammation, and so on.

Kiran Krishnan: And the thing that I was most excited about that is, imagine if they were eating right, imagine if they were exercising, imagine that their stress was being managed, right? What a profound effect it could have. And sure enough, we saw that empirically in the market once we started getting it into the hands of practitioners. So that’s where I’m super excited to see over the next six, eight months, the feedback that practitioners like yourself will give us. Because I think we’ll probably discover other uses of it that we couldn’t see in our clinical trial because those are generally unhealthy people to begin with. I think you guys will find that it affects your patients in an even more profound way.

Dr. Kara Fitzgerald: 100%, no doubt about it. So I just wanted to go back to a comment you made when you were outlining the research. You talked about the joint space changes and I think you just sort of informally likened the joint spaces to 25-year-olds, post-intervention. I mean, have you done analysis where you’re… I mean, because there is some predictable changes. You could use joint space measurements as a biomarker of aging. Did you actually do that and see that with those changes or is that something that you might do retrospectively?

Kiran Krishnan: So we did joint space measurements in the intervention group compared to the placebo group from baseline to day 90. I don’t think we did it at 120 days. So we did baseline to day 90 comparing placebo to treatment group. But what we saw in the improvement in joint space would be equivalent to a reversion of aging, so that fits the anti-aging idea. But I think establishing a longer term way of measuring that would be really interesting. In one of the talks that I’ll do at some of the shows coming up, we have a number of the radiographs in the PowerPoint.

Dr. Kara Fitzgerald: That’ll be cool.

Kiran Krishnan: Yeah, so people can actually see for themselves like, wow, okay, this is the visual change.

Dr. Kara Fitzgerald: Yeah. Yeah. Yeah. Yeah.

Kiran Krishnan: You don’t even have to do millimeter level or micron level measurements. It’s so visually clear between day zero and day 90. It’s mind-boggling.

Dr. Kara Fitzgerald: That’s so fascinating. I mean, I would be curious though to compare them to different ages of normal joint spaces in young adults, middle-aged adults, older adults, et cetera. That would be super interesting.

Kiran Krishnan: Yeah, actually, that’s probably data… So if we took all the treatment group people, we know their ages, right, and we know where their joint space is now at day 90, we could probably compare that. There’s probably some existing data, right?

Dr. Kara Fitzgerald: Yeah, I’m sure that you could access some data like that and really get some evidence on what’s transpired.

Kiran Krishnan: Yeah, well we could give a biological age to their joints, right? Which is really interesting. So your chronological age is this, but your joint is that of a 35 year old now, right? That could be really interesting. That’s a great idea.

Dr. Kara Fitzgerald: Yeah, yeah, yeah. Super interesting. Yeah, well, if you do it, circle back so we can have a conversation on it or I can at least post something.

Kiran Krishnan: Well, if we do it, we’re going to call it the KF measurement. We’re going to call it the KF index of biological joint age.

Dr. Kara Fitzgerald: Oh, that’s really funny. Yeah, I mean, we do it with VO2 max. I mean, we’re paying a lot of attention to appropriate bio age measures and this seems like it really could be one. It could be one.

Kiran Krishnan: Yeah, that’s a very interesting idea.

Dr. Kara Fitzgerald: I think I actually have your WhatsApp. I’ll put it in my calendar to periodically bug you.

Kiran Krishnan: Please do.

Dr. Kara Fitzgerald: Because it’s something that you guys could probably materialize that without too much difficulty. Okay, contraindications for the product? Side effects?

Kiran Krishnan: Not so far, no. And that’s part of the beauty of doing the 1,268, or whatever, patient study, right? That’s one of the reasons we wanted to do such a large population is because that’s where you really see adverse events. You could get lucky in a 60 patient study and not see any adverse events, but we saw nothing. Well tolerated between all these people. These are elderly people and people on medications and things like that. So no, no known contraindications for it at all.

Dr. Kara Fitzgerald: And massive use history for both compounds, right?

Kiran Krishnan: Yes, of course. Yeah.

Dr. Kara Fitzgerald: So you’ve got this data just for millennia, really, basically. OK, so Calroy has a pretty cool suite of products. I’m a massive fan of them. I use Arterosil HP as part of my daily stack, as it is for a lot of my patients. And I actually have a healthy heart so I’m sort of using it off-label for just general glycocalyx management. I think it’s that important of a player. How do you think about using this with some of the other Calroy products?

Kiran Krishnan: Yeah. So actually that was another reason I became very interested in working with Calroy on it, is because as I start to look at overlapping pathologies and then I started digging into prevalence data and all that, statistically it’s shown that osteoarthritis patients have a 50% increased risk of heart disease compared to age matched cohorts who don’t have osteoarthritis, right?

Dr. Kara Fitzgerald: Wow.

Kiran Krishnan: And then same thing with cardiovascular patients. Cardiovascular patients have a higher increased risk of developing osteoarthritis compared to age-matched individuals that don’t have cardiovascular disease. And what that’s telling me is that the pathologies overlap quite a bit because they’re both inflammatory conditions and they’re both driven by similar inflammatory pathways. And then also I can really see where osteoarthritis will drive even more heart disease because osteoarthritis also creates sedentaryness and metabolic syndrome and all that, that also elevates that. So to me, Arterosil and Cartigenix go hand in hand, right? And Calroy has done an amazing job of penetrating the marketplace and supporting people who are concerned about cardiovascular health. Those same people, a good percentage of them probably have joint issues as well.

Kiran Krishnan: And so, as Arterosil already starts to rescue their cardiovascular system from the foundational issues around risk of atherosclerosis and so on, we can also then start rescuing those people from joint issues and getting them mobile again, getting them moving, which will in turn help their cardiovascular risks also. Right. So that significant overlap, to me, was like a beautiful pairing of the two products going hand in hand. And then every cardiovascular patient could certainly benefit from bringing down all those inflammatory markers. So it’s a really nice pairing between the two.

Dr. Kara Fitzgerald: It’s going to be exciting to kind of see where this goes as it’s launched and, to your point, as more clinician data comes forward. I mean, I’m just thinking about the central nervous system and some of the kind of sexy preclinical work coming out on the endothelial glycocalyx and the blood-brain barrier, you know, or at least the fact that Arterosill could tend to it. I think the preclinical isn’t— We see damage to the endothelial glycocalyx, but it’s really exciting that we actually have a meaningful tool. Of course, it seems to me that Cartigenix has to have a role in the central nervous system and we’ll just pay attention and see how that kind of bears out.

Kiran Krishnan: Yeah. For sure. I would be very interested to see how this impacts your long haul COVID patients and people with neuroinflammation. I think that’s a great area that you’re thinking about. And then you throw Vascanox HP into the mix like, whoa, perfusion for all of us, right?

Dr. Kara Fitzgerald: Yeah. Yes, yes, yes. Right.

Kiran Krishnan: And that’s just amazing icing on the cake. And so, I take all three products, obviously, together and I think there’s going to be some really, really interesting outcomes for patients when you get all three of them on.

Dr. Kara Fitzgerald: Good, really exciting, exciting. Let me just ask you about additional products for collagen beyond using this one? I mean, are you a fan of using actual collagen, any particular type, anything else? Like, what’s a good collagen rebuilding protocol for you?

Kiran Krishnan: Yeah, so for me, I think taking collagen, itself, is useful. I think one of the things that one has to really think about in terms of proper utilization of collagen is being mindful of liver health. And the prevalence rate of fatty liver and elevated liver enzymes is just mind-boggling these days, right? It’s a massive epidemic.

Dr. Kara Fitzgerald: Yeah, massive. Yeah. Yeah.

Kiran Krishnan: And the transporting of collagen and collagen peptides to areas where it needs to go to repair the skin and so on, is dependent on the liver in large part. And so I think one of the areas that people really need to be thinking about as we’re thinking about rebuilding joints and enhancing the effects of things like Cartigenix, especially if you’re taking collagen, is what are we doing to support the liver? Are we doing the milk thistles? Are we bringing down liver enzymes? Are we measuring liver enzymes? Are we looking at fatty liver and so on? So I would say that anything that supports the liver would probably enhance the effect of all of this quite a bit.

Dr. Kara Fitzgerald: Interesting. Cool.

Kiran Krishnan: Because the repackaging of collagen into the types of collagen peptides that our tissue can use is the responsibility of the liver and the liver has to be functioning properly in order for that to happen appropriately.

Dr. Kara Fitzgerald: That’s awesome. That’s nice angle to put together our thinking around designing a good intervention package. We’ve covered a ton in this podcast today. I think we’ve hit all the bases. Is there anything that you want to add? Anything that we missed?

Kiran Krishnan: I think one of the things that we’ve actually— We didn’t miss this, we talked about this quite a bit, but I just want to reiterate it. The inflammatory component of this is just… I cannot say enough about the anti-inflammatory effects of this product. And my personal health focus is around cardiovascular health. It’s my primary focus and the reason for that is we have a very strong family history of cardiovascular disease. When I learned about Arterosil, I got on it immediately three, four years ago. But then the other thing I’m always watching out for is inflammation. So I’ve been taking garlic extracts and turmeric and all of those things, which are all wonderful things, but nothing has shown this level of anti-inflammatory effect as a the Cartigenix product, so to me, that becomes one of the real key benefits of this product that shouldn’t be overlooked.

Dr. Kara Fitzgerald: Yeah, good. I appreciate that you underlined that one again. And we’re measuring a good suite of inflammatory markers in clinical practice. Anybody practicing functional medicine is doing that. So data will be forthcoming from our various practices and anybody listening to this, keep us posted. Keep me posted and then we will also make an effort to share with you what we’re learning in our clinical practice as well.

Kiran Krishnan: That’s excellent. Well, thank you so much. Yeah, it’s been wonderful. I’m super excited for this to come out, and I can’t wait to get out there and start talking to clinicians about it.

Dr. Kara Fitzgerald: Yay! I mean, bravo, bravo. Bravo you for bringing it forward to Calory, Kiran, and just thanks for joining me on New Frontiers today.

Kiran Krishnan: My pleasure. Thanks for having me.

Kiran Krishnan is a research microbiologist and a health and wellness expert who aims to make complex information understandable to all. He has founded a number of successful health and supplement companies over the last 20 years including co-founding and leading Microbiome Labs, the preeminent, microbiome therapeutics focused brand among healthcare professionals. He is currently a co-founder and partner in 3 other companies that aim to revolutionize wellness care and an advisor to Calroy Health Sciences. He has conducted and published several research studies in scientific journals, has published chapters in scientific textbooks/references books, has global patents and is a sought after speaker on human health and the microbiome.

Kiran Krishnan

Calroy Health Sciences

Cartigenix HP

Arterosil HP

Vascanox HP

Research: Assessing the effectiveness and NSAIDs sparing effect of celery seeds and Boswellia serrata in osteoarthritis management

Research: Efficacy and Safety of Boswellia serrata and Apium graveolens L. Extract Against Knee Osteoarthritis and Cartilage Degeneration: A Randomized, Double‐blind, Multicenter, Placebo‐Controlled Clinical Trial

Research: Clinical effectiveness and tolerability of Celery seed and Boswellia serrata extract in osteoarthritis

Study: Oral spore-based probiotic supplementation was associated with reduced incidence of post-prandial dietary endotoxin, triglycerides, and disease risk biomarkers

Research: Stress Induces Endotoxemia and Low-Grade Inflammation by Increasing Barrier Permeability

Podcast: Innovative Approaches to Cardiovascular Care: A Deep Dive with Dr. Mark Houston

Podcast: Mastering Cardiovascular Longevity: Glycocalyx & Biohacking for Optimal Heart Health

Podcast: How to Fix the Vascular Health Crisis: The Endothelial Glycocalyx

DrKF Clinic: Patient consults with DrKF physicians including Younger You Concierge

Bio Age Self Assessment Quiz

Younger You book

Better Broths and Healing Tonics book