← The Human Upgrade: Biohacking for Longevity & Performance
The Human Upgrade: Biohacking for Longevity & Performance
Why Women’s Joints Are Failing 10x Faster : 1349
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- [00:00]
Kieran Krishnan
In the U.S. 32% of adults 18 and over have diagnosed osteoarthritis. They're dealing with pain 24 7.
- [00:09]
Dave Asprey
They diagnosed me with arthritis when I was 14 years old. I'd had terrible, terrible knee pain. A lot of modern painkillers accelerate joint damage Kieran Krishnan is a research microbiologist with over 17 years in the nutrition and supplement field. He's led clinical trials showing how a specific blend of two plant extracts can trigger joint repair. Unlike painkillers that only match mask the symptoms.
- [00:34]
Kieran Krishnan
Both our studies we did the first measurements of pain and inflammation in seven days. At the end of the 90 days, what we see on average in almost 2,000 patients in these clinical trials is a 75% on average reduction in pain.
- [00:50]
Dave Asprey
I've used for many years. And it does have positive joint and even brain effects. So how much of joint pain in people today is diet related? You're listening to the Human Upgrade with Dave Asprey. Your phone screen is aging your skin and wrecking your sleep at the same time. Artificial blue light goes from your phone screen straight into your eyes and deep into your skin. That light messes with your melatonin levels, interrupts your deep sleep and speeds up skin aging by breaking down collagen. The bodyguard's Red light converter fixes this at the source. It's a first of its kind screen protector with real tech that converts blue light into beneficial red light before it hits your face. It turns your scrolling into a skincare routine. It supports healthier skin, reduced eye strain, improved sleep quality and fewer screen related headaches. Third party testing showed a 50% plus increase in red light exposure within the optimal range of 620-770nm. And this comes with zero compromise on your screen. The red light converter preserves your screen's true colors and full touch sensitivity. Beyond its wellness benefits, the red light converter provides ultra thin edge to edge protection for your device and bodyguard stands by their quality. Enjoy peace of mind with lifetime replacements, ensuring your red light converter continues to protect and support your biology for the long haul. Visit bodyguards.com and use code Dave for 25% off. That's bodyguardswithaz.com for 25% off. There's a really good chance that you don't get full use of the food that you eat. That's because you're not absorbing it. That's because as you age, even starting in your 20s or if you're stressed, which is pretty much all of us, that means that your enzyme levels drop and enzymes are what turn your food into its components so your body can make full use of it. It's possible to eat a steak, but really only get half the benefits of the steak. Mast zymes are full spectrum digestive enzymes that help you break down those proteins, the carbs, the fats, even the fiber. All you've got to do is take it with a meal so you get better digestion and you can even take it during a fast. And then these enzymes will work on your own tissues to help break up things that you don't need. All you've got to do is go to bioptimizers.com Dave and use code Dave15 and they'll give you 15% off your order of mass times. Kieran, why do people's joints hurt all the time? Despite the billions of dollars that big pharma has spent on this problem?
- [03:31]
Kieran Krishnan
Yeah. And you know, and they continue to spend billions more. In fact, if you look at the trajectory of clinical research and funding that goes towards this, it has gone up linearly over the last 15 years. I think the big reason is because they're really not going after the root cause driver. They're missing a couple of critical points that won't change if they go after pain management side of it. Right. So what they're really doing, what they're trying to do, and then a lot of natural products have tried to do this as well, is just mask the pain. And when you mask the pain, you're really kind of masking a pathology that is progressing very aggressively. And when we dig into what's actually happening in the joint, it becomes really clear why this is a progressive condition and why actually masking the pain, if that's even successful, actually it has a detrimental effect on the, on the, on the health and the longevity of the joint.
- [04:27]
Dave Asprey
Are you saying that a lot of modern painkillers accelerate joint damage?
- [04:32]
Kieran Krishnan
It can, yeah. Because one aspect, right, if you think about it, it's, it's so counterproductive. It's, it's no different than like the idea of you have reflux. So why don't we, you know, reduce your stomach acid? Well, when stomach acid is actually a condition of too little reflux is actually a condition of too little stomach ac. So the pain is signaling to the body that something is wrong in that joint. Right. And use of the joint and stress on the joint increases the pathology of what's happening in there, that degrades the joint. So if all we're doing is trying to mask the pain and they're continuing to use the joint and putting load on it and so on, we're just accelerating the stimulus that drives the progressive degeneration, you know, so it just, it really does not help anyone. And then we saw in one of our clinical trials that the pain masking barely even works. People barely even feel it, even after years of taking, you know, high doses of these opioids.
- [05:37]
Dave Asprey
Wow. So no benefits.
- [05:40]
Kieran Krishnan
No benefits at all. So in fact, and maybe this is a good time to explain it. So in our second study that we did, so we have, we have two large randomized published studies on this. And then the second study, this was in rheumatoid arthritis patients. Patients. And of course, the ethical boards require that when the patients are coming in because they've been off their meds for the purpose of the study, when they come in, and if they complain too much of pain, you have to put them back on the medication. It's called rescue medication. Right. And in this case, it was a very well known opioid, 200 milligrams a day, so a pretty strong dose. And the study was double blinded. So a number of patients, as they were coming in for each of their visits, started complaining of pain and had to get put back on the opioids. Now, when we unblinded the study at the end and we looked at the different groups, as it turns out, virtually 100% of the placebo group was back on the opioids, more than half of them about 45 days into the study. So about halfway into the study, and in the treatment group, 10% were back on the rescue medication. Which means that for a good portion of the study, for half the study, we were going head to head against people who are on full dose prescription opioids. And when you look at the placebo group, which is who ended up back on opioids, when you look at their data on pain and inflammation and mobility and all that, nothing changed. Right. They were just a straight line of pain and dysfunction without reducing, in terms of reducing pain, it didn't get worse, but it certainly didn't reduce at all. Right. So that was really surprising to me because you figure if they're back on their medication that they're reporting that their pain is reducing and so on. None of that, we didn't see any of that.
- [07:34]
Dave Asprey
That's profound. So it's a whole different way of looking at joint pain. Are we in pain because we have toxins that cause inflammation or because we have crystals like uric acid or oxalic acid from our Food or is it because of some sort of an immune response that's breaking down our knees or our other joints?
- [07:53]
Kieran Krishnan
So that's actually a great question. So when you look at arthritic based pain, especially in the knees or any of the load bearing joints, the hips and so on, that is often one of two pathologies. Pathology number one is it's a rheumatoid like effect, meaning it's an autoimmune effect. Right. So there's inflammation, there's damage and a trigger in that joint space. Then your immune system mistakenly identifies your own tissue or your own proteins as the culprit and starts attacking it. Now, it is very clear that even that pathology is often driven by inflammation. And that pathology would not exist had you not had a precursor, which is the inflammation. The second pathology, which is actually even more common, is the osteoarthritis pathology, which is 100% driven by an inflammatory milieu that builds up in that joint space. Right. And that inflammation is actually global inflammation. It's the same inflammatory markers that are driving lots of other chronic conditions. So the ones in particular are TNF alpha, IL1, IL1, beta and alpha, and then IL6, interleukin 6, which we talked about in the past in other programs related to the gut and for listeners.
- [09:14]
Dave Asprey
These are called inflammatory cytokines. And these are different inflammatory signaling markers. And different types of inflammation have a different signature and therefore different ways of treating them. And when you hear just the normal health influence, like inflammation is the driver of everything, that's like saying liquid is the driver of everything. Was it water or was it diesel? Because they're kind of different liquids. Right. So oversimplifying doesn't work, but making it too complex doesn't work. So IL6, which is the most important of the cytokines? I would argue that's the one. If you had Covid or long Covid, that goes crazy. In fact, it seems to be the most prevalent one in chronic and acute conditions. Right?
- [09:57]
Kieran Krishnan
Yep.
- [09:57]
Dave Asprey
Okay. So this is one that's tied to joint degradation, but it's also gonna cause brain fog and it's gonna cause skin conditions and everything else. It's a nasty one.
- [10:04]
Kieran Krishnan
It's a nasty one. And anxiety, it's a root cause driver of anxiety and HPA activation. It plays a big role in leaky gut and inf. Leaky gut is a big source of it. So we know that there's a number of things that we do in our lifestyles that drive this kind of inflammatory cascade. And then here's what's so interesting and why this becomes a progressive condition. So within the joint space, you've got something called the articular cartilage, right? That's the cushioning in the joint. That's what keeps the bone on bone from rubbing and which will then lead to pain. If you have bone on bone rubbing. So you've got the articular cartilage and it's providing the fluidity, the lubricant, and also the cushioning. And arthritis is defined as a progressive loss or degeneration of that cartilage, right? And then eventually you have the bone and bone rubbing and pain and so on. And so what's actually happening is you've got these cells in that meniscus or in that. Sorry, in that synovium, which is that gap, that space in between the joint, that are called chondrocytes. Now, these chondrocytes are these amazing anabolic cells that continue to build and rebuild and repair the cartilage, right? Because we're gonna damage the cartilage, the load bearing, the movement, all the good stuff that we wanna do, right? The walking and hiking and lifting and all that, that's gonna damage the cartilage. And so your chondrocytes are there to constantly rebuild it. They take collagen, they lay down collagen type 2, they bring in the right fluid and so on. Now, when you build a certain level of these inflammatory cytokines that we Talked about, so IL6, TNF Alpha and IL1 in particular in that synovial fluid, and you're bathing the chondrocytes in that synovial fluid, they actually end up having a phase shift where they go from a anabolic cell to a catabolic cell, right? So they completely change. They have an epigenetic change to stop building the joint and in fact start degrading the joint. They start expressing things like MMPs, which are matrix metalloproteinases, and all of these enzymes that eat away at the cartilage.
- [12:23]
Dave Asprey
How old do you have to be for that to start?
- [12:26]
Kieran Krishnan
Typically in your late teens, early 20s. That is evident in a certain portion of people. There have been a couple of studies on this. So one of the studies is called the Framingham Study on Arthritis, right? So they took asymptomatic people who've never complained of joint pain, 50 and over, in this case, and they did MRIs on their joints, and they found that 90% of people, 90% of them had arthritic pathology already happening in their joints in at least one joint, about 70% of them had in more than one joint. Then other studies have looked at people over the age of 14, and they found that the majority of people had some degree of arthritic process going on in their body, right? So it's like this, which you and I know about aging a lot. We think about aging a lot, and we think about this battle between catabolic and anabolic processes in your body, right? And if you end up with a net catabolic, which is a breakdown process, then you're breaking down faster than you can rebuild. And that's one of the issues and the hallmarks of aging. And so we're undergoing this catabolic anabolic battle in the joint. And it's representative of other similar processes happening in the body, because the drivers, IL6 TNF alpha, IL1 beta, drive that same shift in your brain, in your nervous system, in your gut, in your muscles and other areas as well, right? So if it's happening in the joint, it's a canary in the coal mine that, okay, this is happening elsewhere in the body as well. So now you've got the chondrocytes that have shifted from being the building cells which are anabolic, to degrading cells, which are catabolic. And then not only do they go into this active catabolic mode, they themselves can release more inflammatory cytokines, right? IL6TNF alpha and so on, and they can become senescent, which means they do nothing. They just sit there and they're not really helping or hurting, but they're certainly not rebuilding. Right? And so, and then the other problem with it is that that joint space, the cartilage and the chondrocytes, don't have its own blood supply supply. So it's counting on blood and new things coming in, washing out that fluid and all that by diffusion from supplying the bone in the local area. And so there's diffusion from the micro vessels in the bone that the articular cartilage is counting on for circulation. So then as we get older and we have more inflammation, then the lining of the vessels also fall apart, which means that we don't get really good microcirculation. And as a result, we can't wash out all that inflammatory milieu that's in there, right? So it's a really great description of the type of inflammatory based catabolic aging process that occurs in so many parts of the body.
- [15:22]
Dave Asprey
If you target all of those pathways in your joint to cause it to start regenerating, how quickly does it work?
- [15:30]
Kieran Krishnan
That's A really important question we wanted to answer. So in both our studies, we did the first measurements of pain and inflammation in seven days. And then we progressed every seven days or so up to 90 days. And then in our second study, we followed the patients all the way out to 120 days after ceasing all of the treatments, placebo or the product. What we found is that within seven days you can start to see a metabolic shift in cartilage, rebuilding and degeneration. So there are markers that you can follow that indicate rebuilding or degeneration. The markers of degeneration are well known. They're called ucctx, which is urinary CTX and sctx. Right, Serum CTX and then another one called comp, C O M P. And so if you look at their levels in the body, it's indicative of whether you have a net breakdown process. And then the, the converse to that is P2ANP and P2CP. These are the rebuilding ones. So when we're looking at those markers, we start to see that in seven days we can start to see a reduction in the overall inflammation. And as a result of that, a flip, or at least the starting of the flip of these degeneration versus regeneration markers. So the body is really quite incredible, right? Given the right condition, you can make profound alterations in the processes that are happening in a relatively short amount of time. Now, that's not gonna stick. If we just do it for seven days, then we follow it over 90 day period. And at the end of the 90 days, what we see on average in almost 2,000 patients in these clinical trials is a 75% on average reduction in pain, a massive reduction in those critical inflammatory markers. And then we also measured high sensitivity CRP and then sedimentation rate, which can also give you an inflammatory kind of picture of the body. And we see a 50% reduction in the degeneration markers and about a 45, 50% improvement in the regeneration markers. And most people reported an alleviation, at least a start of the alleviation in pain in seven days. Sorry. So in a week you could start to make a significant amount of change.
- [17:48]
Dave Asprey
And this is from what, two capsules a day?
- [17:51]
Kieran Krishnan
Two capsules a day, yeah. And so it's 550 milligrams per capsule, so 1,100 milligrams per day of a very unique blend of celery seed and boswellia. And there was a lot, this is about 12 years plus in the making in terms of the discovery phase of it, because it's so much more than what most people will understand about celery and boswellia.
- [18:20]
Dave Asprey
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- [21:39]
Kieran Krishnan
Yep.
- [21:40]
Dave Asprey
As a. As a supplement. I don't know much about it. And what's so unique about your blend? I mean, couldn't anyone just do it?
- [21:47]
Kieran Krishnan
I guess they could if they had the right team in a decade or so, but. Okay.
- [21:53]
Dave Asprey
It's not just these two ingredients that. Because there will be people who hear this. Go. I'll sell it on Amazon. It's not the same, but I don't know why.
- [22:00]
Kieran Krishnan
Right. Yeah, no, that's a very important question. So let's take a Boswellia first. And Boswellia generally is really good for you, as you mentioned, because most Boswellia products are standardized to something called boswellic acids. They're often abbreviated akba. So if you look at good Boswella Boswellia products on the market, they say 30% or 35% AKBA. The AKBA are what we call LOX inhibitors. Right. So they are inhibiting the lipo oxygenase, which is the inflammatory pathway. So that's great. And that has lots of benefits throughout the body. What's special about our version of Boswellia is we took the plant apart and we spent a lot of time trying to identify new actives within the plant. Because nature and plant chemistry is far more complex than we can wrap our head around, right? And Akba and all were identified like 40 years ago. So we're like, analytical chemistry has become better and more sensitive since then. So we're like, let's dig into this a little bit better. So we found a couple of different actives. One of them is called serotol and the other one's called terocalic acid. And serotonin and terocalic acid, we took them apart and then we started studying them specifically to see what kind of effects they may have. And we found that serotonin has this ability to switch the switch on tissue degeneration to regeneration, right? And that's an epigenetic shift because when you start activating MMPs like matrix metalloproteinases and all that, that means the body's going through a breakdown process that happens when we get trauma and injury and all that, right? So we see that. And so we started studying the effect of serotol and we see a reduction in those catabolic enzymes and an activation of an anabolic process. And we said, wow, that's really interesting. That may move the needle on the repair side of things. And then the tyrakelic acid is really interesting as well because what we found is that very preferentially reduces IL6 and TNF alpha, right? And TNF alpha is a little bit upstream of IL6 because it's one of the first things that gets activated by receptor binding on things like macrophages and mast cells and so on. And so it has the ability to reduce this at the upstream level. So you get TNF Alpha and IL6 coming down. And we know that those are the two really important culprits, right? So we said, okay, our boswellia can induce repair. And our boswellia now has very specific anti inflammatory function to those targeted cytokines. Then we looked at the celery seed. And the reason we brought the celery seed in is because it's a product that was worked on by Procter and Gamble 30 years ago. They were working on this product for large animals that had hip dysplasia and severe pain and all that. Large breed dogs, they actually found that right type of celery that had the right hydrocarbon profile grown in the northern part of India. And so our partners, who had a separate company, partnered with Procter and Gamble to do the extraction and figure out this source material. Procter and Gamble, a little bit of a sad story, they decided to drop the product Many years ago. Because the office that managed that particular project was in one of the Twin towers. Right. In 9 11. Yeah. So they did 3,000 pages worth of animal based studies on this product with our partners in India. And then the team that was managing that obviously went through that horrific thing. And so Procter and Gamble just said, we're just dropping this project. And they said, here you could take all the technology that was started. Our team then took that and then from that point on started working on developing that into a human product because of the upcoming and looming opioid and other crisis. So they were looking for a much stronger natural pain anti pain medication, which is a COX inhibitor that does not have all the side effects of normal opioids and COX inhibitors and does not have the GI disturbance effects. Right. So they isolated three main compounds from the celery seed, which took more than 15 years to figure out. And then those are the three main compounds that go into the product to provide really effective toxin inhibition.
- [26:34]
Dave Asprey
So it's a super precise, like a distillation of what's in them. Because regular celery has a bunch of toxins. You don't want to eat a lot of celery seed.
- [26:44]
Kieran Krishnan
Totally. Yeah.
- [26:44]
Dave Asprey
You're taking out the good stuff, leaving the bad stuff. Okay, that's, that's phenomenal. And that combination, what do you see for things that, that really are, are on the ground tests like walking distance, like what happened there?
- [26:58]
Kieran Krishnan
That's a very important point you bring up. And to me that's where like the rubber really hits the road on some of these things. Right. So there's a very standardized test called a six minute walk test. The six minute walk test is a well established way of quantifying functionality. So what we did is we took all these individuals and of course in both the placebo and the treatment group, blinded. And they did baseline six minute walk tests. Then they did it at the 90 day period. The placebo people, and keep in mind, most of them were back on their prescription medications at that 90 day period, did not improve the distance they covered in that six minute period at all, not by a single step. But in the treatment group they increased it by almost 60%. Right. The distance that they could walk. And that's where the rubber hits the road for me. Because it's like that's the difference of being able to now walk to your mailbox and get the mail and go for a walk with your family or take your dog on a walk. And those types of things that really end up mattering to people in their lifestyle. And so when I saw that part of the data, that meant way more to me than the biomarkers and all that, which are very compelling.
- [28:13]
Dave Asprey
End of the day biomarkers can be good, but results are bad. It doesn't matter. So you've got something that's truly unique. How does this compare to what people are spending on joint pain specific drugs?
- [28:26]
Kieran Krishnan
If you look at what the average person who's dealing with osteoarthritis is spending, so they're typically taking pretty high doses of things like glucosamine, MSM and so on. Right. So they're spending about 60, $70 a month on those supplements. Then they're taking NSAIDs. We see that over 75% of people who are on prescription pain medications for their joint pain still use NSAIDS to try to get through the day. Right. So they're Advil and Tylenol regularly. And then of course the prescription pain medications, depending on the version they're taking and their insurance, they could be spending anywhere from another 40, $50 a month in co pay all the way up to 2, $300 a month in their copay. So I would say the average person is probably taking six to ten capsules a day at least and spending a minimum of 200amonth and getting virtually no benefit from it. Right. Like it's not improving their distance taking cover, it's not improving their functionality. They're dealing with pain 24, seven, as you did when you were younger. And we know that that pain creates this hopelessness feeling. Right. And that leads to depression in many of these people. And then the World Health Organization actually has now established that osteoarthritis is the second leading cause of disability worldwide. Right. So people are losing the freedom of movement. And we all know that movement is one of the most important thing to maintain longevity and health span, you know. So yeah, it's really a baffling issue that has so many downstream effects that is really mistreated right now.
- [30:17]
Dave Asprey
That kind of blows my mind. $200 a month and there's millions of people who are just in constant pain from these joints that are breaking down. And cardiogenics, the stuff you make, which is just a new creation in the world. What does it cost for a bottle?
- [30:35]
Kieran Krishnan
I think retail, it's somewhere in the 70s.
- [30:37]
Dave Asprey
Okay, so it's not crazy expensive for a supplement. Not at all. I, I trust you to do really good science because it's got to be like 10 years ago I came across Arturasil Yeah. And I've done a whole episode with you on that where there's really good clinical science showing you can protect the lining of your arteries. So I've been on that stuff forever and I know it really works. And you've come out with, like, consistently different things. Your nitrous oxide blood pressure stuff, it was so powerful, I can only do a half dose or I don't have enough blood pressure. So that would be a sign that it works. It's actually crazy effective. So when I heard about this, I don't normally have joint pain anymore, but it's taken enormous changes in my diet and just my whole lifestyle. And if I do get them, I kind of know what I did to deserve it. But this is one of those things where I still feel like I have maybe regrowth of cartilage or I still have room for improvement, or certainly prevention. If people have reasonably okay knees and they go on cardiogenics, is it going to just stop any further decline or will it actually help you grow things back?
- [31:53]
Kieran Krishnan
Yeah, and that's a really important perspective. Right. So we believe very strongly, and we have good, good data for this, that it'll actually regrow your knees. And we know so that in fact, there's big population studies and we actually have X rays of all of the people in our second study where you can look at the joint space, and you're looking at the reduction in the joint space in the X rays. And that reduction in joint space can be measured as a biological age factor. Right. As you reduce joint space, it's actually accelerating your biological age. As you increase joint space, you're reversing the biological age. So we saw a very significant reversal of biological age in that sense. And the way I think about it, right, is that this is one of the critical areas that we want to be very preventative in our mindset, because we do that with our brains, we do that with our cardiovascular system and all that. We wouldn't think of starting interventions in our brain health once we start getting early signs of dementia. Right. We really want to avoid that from happening. So I always tell people this is one of the areas you really want to not end up with symptoms, because if you're ending up with symptoms and things start to hurt, that means you've already allowed that pathology to go far enough, and now it's going to be even harder to bring it back. Fortunately, you can with the cardiogenics, but really think of the cardiogenics as like a prevention aspect of joint and Structural health. Right. Because we're really thinking about our whole structure that carries this body around and all the things we want to be able to do with it.
- [33:38]
Dave Asprey
What does this have to do with mitochondrial function? Are they controlling our joints?
- [33:43]
Kieran Krishnan
Yeah. So the chondrocytes tend to have very high numbers of mitochondria per cell. We know that. We look at all the different cells that have mitochondria in, and virtually all cells, except for red blood cells, have it. Muscle cells, for example, have very high concentration of mitochondria because they're so energy dependent. Right. So they have to produce a lot of ATP to do their functions. Same thing with chondrocytes. So chondrocytes require a lot of energy to synthesize the collagen and rebuild and do all of the stuff that they do similar to muscle cells. And so as we age, as we build up toxicity, as we build up inflammation, we're choking out the mitochondria in the chondrocytes, and that also accelerates their degeneration. So anytime you can improve circulation, anytime you can improve nitric oxide, where the Vasconox comes in handy in this as well, anytime you can improve mitochondrial function, we're going to be supporting the joint.
- [34:42]
Dave Asprey
I think most people miss that. And mitochondria and brain mitochondria, heart mitochondria, muscle. But the fact that joints themselves, the repair mechanisms, are very dense with mitochondria, that's really important to understand. So it could be why someone isn't feeling great in their joints just because their mitochondria suck. And you gotta fix those. Okay, totally.
- [35:02]
Kieran Krishnan
Yeah. And, you know, at the end of the day, when I look at the joint and I dig into the research more, it's really a canary in the coal mine, because what's happening, we mentioned this earlier, what's happening in the joint, the degeneration process is very telling of similar degeneration processes happening throughout the rest of the body. That's why there's a very significant overlap between joint health and cardiovascular disease. Right. So, for example, people with rheumatoid arthritis have two times higher likelihood of developing cardiovascular disease. People with cardiovascular disease have 50% higher risk of rheumatoid arthritis or osteoarthritis in particular. Right. They're both inflammatory conditions, they're both progressive inflammatory conditions. The vascular system plays a role in both of them, and they're Both driven by IL6, TNF Alpha, IL 1 beta. And so that what's happening in the rest of the body is Very similar to degeneration that's happening in the joint. And so when we measured the inflammatory mediators and all that as we're improving the joints, we didn't measure it in the joint, we measured it globally in the body. Right. So another way of thinking of cardiogenics is a product that can systemically alter the inflammatory milieu within the system and that has benefits to all kinds of things. Right. And then you pair that with the arteriosil which is taking care of the cardiovascular system, which is delivering nutrients and food and all that to all the body. The vascanates which allows for nitric oxide to provide vascular compliance and proper dilation and immune support and all that. And then the cardiogenics which is doing this complete global restructuring of the catabolic anabolic processes and the inflammatory processes between the three, they're really taking care of a lot of things.
- [36:59]
Dave Asprey
That is a really, really good explanation of why I actually do use all three. Because I kind of like just the way you put it together scientifically. If you're listening to this and you're saying, well Dave, tell me everything you take. No I won't. I'll tell you why I take things I take one at a time. But if you just copy me, you probably don't have a history of arthritis when you were 14, a history of obesity, and you're probably not a 6 foot 4 white dude. Like all these things are highly relevant. So I'm going to teach you from the world's best. So here's why to do this. If you want this goal based on who you are, where you are, all that stuff matters. So sorry it's more complex than you want it to be, but I'm glad you're not copying me directly. However, I will teach you all that stuff in the AI that we're working on with Upgrade lab. So like there is hope, you don't have to do everything. But if joint pain is a thing, you could try a low cost product. It's about 70 bucks. It's calroy.com and cardiogenics and take it for a week and see if you see some changes. The odds are pretty high. Is calroy.com Dave is you get a discount for that. I have a question though. Glucosamine and chondroitin, age old supplements for knees, are they just dead in 2025.
- [38:10]
Kieran Krishnan
You know, meta analysis came out that looked at, I think it was 17 studies on glucosamine and basically they found no actual effect on joint health. So no changes in the markers we talked about. So the degeneration markers, the UCCTX and SCTX and comp and no change in the regeneration markers. And so it's not. Not fixing the problem. And people spend literally billions a year on those. Because if you think about the biggest retail joint health products, the biggest one I know sells about 400 million a year in retail. The second biggest. This is a supplement. Yeah. That you find at all the drugstores and big box stores and all that. So people are literally spending billions a year on something where the meta analysis studies show that that's not really doing anything. And then. Same thing with all the prescription stuff. Right? Not really doing anything. And this is why the prevalence rate of osteoarthritis is so huge right now. If you look at adults 18 and over in the U.S. 32% of adults 18 and over have diagnosed osteoarthritis. Right. Which means they're already symptomatic. You could see it on X rays. There's already joint degradation, cartilage degradation happening now and then. Keep in mind, the Framingham study showed that in asymptomatic people, 90% of them had joint degradation happening, which they just didn't feel yet. Right. So I would say the vast majority of adults over the age of 18 have some degree of joint degradation happening. And up till now, there hasn't been a solution for it, you know, and it's the second leading cause of disability. So it's like everyone is on this road to potentially being disabled and doesn't know it. Right. And doesn't have a tool to do anything about it up to this point.
- [40:12]
Dave Asprey
So if someone just did a lab panel of cytokines and just had, oh, my IL6 and NF Kappa beta are high, the two of the common ones, should they just immediately assume, oh, take cardiogenics, because it's probably joints, or are there other reasons they these would be high without affecting the joints or it's pretty much high. IL6 equals your joints are going in the wrong direction.
- [40:32]
Kieran Krishnan
Yeah. So if your IL6 is consistently high and your NF Kappa B TNF Alpha all consistently high, you can presume that there is some catabolic function happening in your body. And because your joints are a stress point in your body, it's likely that the joints will take the brunt of that type of catabolic effect. Right. So. And it's important for people to understand that when you have global inflammation, which is measured, of course, through blood samples and serum, the inflammatory cytokines migrate towards areas of stress. And so just like if you get trauma somewhere in your body, you get injured, you put stress on your joints, you're lifting, you're walking, you're hiking, that's where it's going to concentrate. This is also why you asked this question earlier about the uric acid crystals. Right. 90% of time people end up getting uric acid crystals in the lower extremities accumulating in their big toe or in the joints in the feet in particular, because those are areas that are experiencing a lot of stress. So there's a filtering of all the inflammatory and toxic compounds towards the areas of stress. The other problem with the big toe is it's also colder than the rest of the body. And the uric acid crystals form faster when it's colder. So that's why it doesn't form closer to the core temperature. But nonetheless, anytime there are areas of stress like weight bearing joints, you're gonna get a concentration of the inflammatory markers that way. So if you got a test and you see elevation of all those cytokines and you can assume that if you're a relatively active person, that some of that concentrated function is occurring in your joints.
- [42:18]
Dave Asprey
Is there imaging that works for joints?
- [42:20]
Kieran Krishnan
If you're asymptomatic, you will need an MRI to really see the progression of the arthritis. If you're symptomatic, often you can just see it with an X ray or radiograph. X rays are not clear, it's our old 80s disposable camera kind of imaging. But in our study, for example, in these individuals you can very clearly see joint degeneration and regeneration even with just X rays. But what you really need is MRI to understand that. So people are now getting more and more the full body MRIs and things like that. So that'll pick it up if you're having some sort of issue.
- [43:04]
Dave Asprey
Mine definitely picked up that I've had multiple surgeries on my meniscus.
- [43:08]
Kieran Krishnan
Oh, and another very important point on that, you know, so this problem of an inflammatory driven degeneration of the joint tends to affect men more up to a certain age. Then when you hit your mid-40s, women accelerate in being affected by this way more than men do at a 10 to 1 ratio. Right. So when you look at adults reporting new joint pain and new joint degeneration between the age of 45 and 55, it's 10 to 1, women to men before the age of 45 it's more men. And then at that, that perimenopause Level through menopause, it significantly shifts towards women. Then the question may be why? Well, women are going through a massive inflammatory change in perimenopause. Right. As estrogen and a lot of the other sex hormones reduce and their gut's becoming more leaky, their metabolic system is changing, they end up with an increase in net inflammation, which is also why they start undergoing higher risk for osteoporosis, cardiovascular disease, and all the other inflammatory driven conditions. So if you're a woman and you're in your 30s and gonna be approaching perimenopause in your early 40s, you have a much higher risk of developing these types of conditions as you go through your 40s. So it becomes really important for women to pay really close attention to it way before that happens. The last thing women need who are going through perimenopause and dealing with all the shit changes is more pain. You know, it just, it shifts a salt on the wound.
- [44:51]
Dave Asprey
In that case, I like to see women at about 35 at least start taking DHEA and pregnenolone.
- [44:59]
Kieran Krishnan
Yeah.
- [44:59]
Dave Asprey
Maybe progesterone. Based on their labs or even if they just have symptoms, you don't have labs, you could do that just based on the preponderance of evidence, which keeps the inflammatory stuff down that comes from cortisol and adrenaline activation. And I think that's gonna, it's gonna give you a much better chance of not getting all this joint pain later in life. And then what you're saying is, you know, at a certain point, you probably want to go on cardiogenics because I think you're marketing it. I'm just reading your, your thoughts here, but you're marketing it for this specific use case. But it seems like it's a general broad spectrum anti inflammatory that maybe goes a little bit beyond just joints because so many of these markers, like if you have brain fog, your IL6 is gonna be high. Right. And maybe it's coming from the joints, but I think you're suppressing IL6 globally, not just in the joints, and you're just seeing the benefit in the joints. Is that real?
- [45:52]
Kieran Krishnan
Totally. Yeah. All the measurements in our studies are global measurements throughout the body. So we're just pulling in a serum and blood from the arm like any other blood draw. And that's where we're looking at it. Right. So we're not going into the synovium or the synovial fluid because our interest was really around, you know, if we can make a shift in global inflammation, does that have an effect on the joint, and it will. And then given the specific ingredients that we have within this product, in particular serotol, turochelic acid, apin and so on, they specifically then modulate the repair and degeneration process. Right. So we're going about it in a multi pronged approach, but you're totally right in that you really can look at this as a global inflammatory product. And as I mentioned, we also significantly reduce high sensitive CRP and esr, which is a sedimentation rate.
- [46:52]
Dave Asprey
Wow, those are really important.
- [46:54]
Kieran Krishnan
Those are really important. Right? And if you look at anyone, for example, one of the earliest measures of risk of autoimmune conditions is elevation and sedimentation rates. That's a super cheap test that anyone can do for almost free. If you have insurance or if you don't have insurance, I think it's eight or ten bucks to do the test. And that will tell you that your body's moving towards this propensity for all kinds of autoimmune dysfunctions. So it was amazing to see that reduce very significantly as well.
- [47:26]
Dave Asprey
I would say I had terrible joint pain, not just in my knees, I would get it in my back, L4 L5, my upper back shoulders for many, many years. And I realized that if I got my diet to avoid the common triggers, that my joint pain would go down. And one of our, one of our live audience members just commented, you know, at an advanced age, you know, very little joint pain or stiffness based on the bulletproof diet, still do it and like, it's all gone. So how much of joint pain in people today is diet related?
- [48:02]
Kieran Krishnan
That's a really important question. So I think diet becomes one of the most, the most prominent source of inflammatory mediation. Right. What you eat, what you're exposing yourself to, what you put into your system has a profound effect on what types of inflammatory markers increase. I published a number of studies around leaky gut. And what we found is that when you eat, eat highly processed, really calorically dense foods, and this is how we would induce leaky gut in people. We'd give them gas station pizza, for example, or a fast food breakfast, right. We would sit college students down and do this and then look at inflammatory markers. What you see within four or five hours of feeding those meals, that you get about a 4 or 5x increase in IL6, TNF Alpha, IL 1 beta and NF Kappa B in those individuals, you can measure it. And if their gut is really messed up, meaning that it has a high propensity for leaky gut, it can take up to two weeks for their inflammatory markers to normalize from a single meal.
- [49:13]
Podcast Narrator
Whoa.
- [49:14]
Kieran Krishnan
That's how profound it is. Right. So imagine they're doing this two or three times a day. It never comes down. And so that's what's setting the stage for this, this big catabolic anabolic battle. And I would say it's probably one of the most prevalent drivers of the inflammatory milieu that leads to joint and other dysfunction.
- [49:33]
Dave Asprey
So if you're doing a four or five day fast, you're probably going to get beyond that window. But you could stack a fast with cardiogenics just to suppress those things even more quickly. Have you ever experimented with that?
- [49:44]
Kieran Krishnan
So I do that naturally. So I'll fast 24 hours periodically. I do do an intermittent fast most days. So I find that to be very beneficial for myself and especially if I need kind of a reset if I've been traveling and I've been making more bad decisions on diet and things like that than I normally would. One really effective reset for me is coming back doing the Vascanox, the nitric oxide. Right. So really improving circulation and getting things flushed out. Arteriosil, which I take regularly anyway, and then I'm on the cardiogenics and the fast really helps kick in some of that kind of repair, regeneration process. So I think it's a great thinking to look at stacking in a fast into someone's protocol with this because yeah, diet and the processing of food alone can be inflammatory, especially if your gut is dysfunctional. Right. And most people's gut, gut are dysfunctional. And I'd say the gut is probably one of the main sources of this global inflammation that we've been talking about.
- [50:53]
Dave Asprey
So you're one of the top experts on inflammation in the body. I would say now someone's holding a gun to your head and they're saying you can eat the big plate of french fries cooked in two week old restaurant canola oil or you can smoke the organic tobacco cigarette. You have to pick one. Which one will it be?
- [51:14]
Kieran Krishnan
I would probably smoke the organic tobacco cigarette because. Me too. Yeah. Number one, it'll probably be a little bit more enjoyable. And number two, I think the lasting effect of that one meal versus the one smoke, the one meal would have a more profound, lasting effect because it triggers a bigger cascade of dysfunction throughout the body that then affects your brain and your joints and your muscles and everything else, you know, Whereas the smoking is probably much more concentrated towards the lungs. And then the lungs can, you know, will repair as long as you're not doing it every day and you're getting.
- [51:51]
Dave Asprey
Eight hours of inflammation from all that smoke, which is bad for you, versus at least 48 hours and maybe five days of inflammation from the dumb french fries. Right?
- [52:00]
Kieran Krishnan
Totally. Exactly. Yeah. So I think that neither one is great choices, but. But the lesser of two evils I would say in that would be the smoke because of the long lasting effects of that inflammation from the fries with oxidized fats and so on.
- [52:15]
Dave Asprey
How old are you right now, Karen?
- [52:17]
Kieran Krishnan
I'm 48. 48.
- [52:18]
Dave Asprey
Okay, so you're doing great. What does your movement practice look like in addition to cardiogenics? Do you do yoga, tai chi, bendy? I don't know, some kind of stretchy thing.
- [52:30]
Kieran Krishnan
I wish I was more bendy and stretchy. Actually, one of the things I've incorporated recently that I've been trying to be diligent about was this idea of movement snacks. Because like many of us, I end up sitting at my desk a lot. Right. I'm doing a lot of my work is at my desk. So then I have this alarm set to move and practice certain movements every, say, 20 or 30 minutes. The movement I like to practice is with a kettlebell. So kettlebell, like sumo squats and kettlebell swings, which basically gets the entire body, just a few of them, you know, a few reps, seven to ten of them, and then like a little bit of a wall sit. I am focused on the 10,000 steps at least. I am also really focused on the postprandial walking.
- [53:20]
Dave Asprey
Oh yeah, postprandial is so interesting. But do you know where the 10,000 steps came from?
- [53:25]
Kieran Krishnan
Yes, yeah, yeah. I mean, it's an interesting. There's a new study that actually shows lowers the minimum there around 7,500. Right?
- [53:37]
Dave Asprey
Yeah, the 10,000, like the first fitness tracker in Japan, made it up in the 50s. So yeah, 7500 seems more scientific. And then there's the Japanese high intensity interval walking. Have you come across that?
- [53:52]
Kieran Krishnan
Yes, yeah.
- [53:53]
Dave Asprey
For postprandial. That's kind of fun, right?
- [53:55]
Kieran Krishnan
It totally is, yeah. And the postprandial is really interesting because the most recent studies I've seen on it, the amount of reduction on postprandial glucose and insulin response from just walking or moving for 10 to 15 minutes is so profound. Right. And it makes so much sense when you think about evolutionarily. Our ancestors never ate and just sat around after that. They ate and they had to get out of wherever they were gathering and hunting things. And they're always on the move so it makes sense. And those are the things I'm really focused on. I do a good amount of resistance training, but I'm trying to get a lot more efficient about that. I don't have time to be at the gym five days a week doing 45 minutes of lifting.
- [54:44]
Dave Asprey
Join and upgrade labs, man. That's what we're all about, is I don't want to waste time in the gym. I don't have enough time, but I will whatever I have to, right?
- [54:51]
Kieran Krishnan
Yes, exactly.
- [54:52]
Dave Asprey
So what's your minimum amount of weightlifting time per week that's effective for you now?
- [54:56]
Kieran Krishnan
I was following this protocol, actually. That helps help. That I found really had profound effects on muscle building and strength for me. And I would do eight minutes twice a week. Right.
- [55:09]
Dave Asprey
Is that so?
- [55:10]
Kieran Krishnan
Good. That's it. Right. I did four movements, really, really slow heavy weights. So I would basically do a squat, so two push pull movements. Right. So I'm doing a upright row, a bench. Right. Typically on machines, because it's easier to control the weight and the movement and the eccentric and concentric movement. And then a leg press and then an overhead pull down. And so the four movements, it's basically about four reps of each movement. But heavy weight, really slow, and just aching your muscles to full failure and then providing like 5, 6 days of recovery and then doing it again. And I found that to be so effective in terms of muscle building and strength. And I saved myself, like, hours in the week, right? Yeah.
- [56:08]
Dave Asprey
These are hours that you had other things to do. And I mean, full respect to people who want to go to the gym every day because you love it, you have community. It's just not necessary if your goal is to have adequate muscle mass and have functioning joints and all. But I do want to understand that interaction between lifting weights and joint health versus going for a walk. So what does lifting heavy and slow do for your joints versus your bones versus your muscle?
- [56:36]
Kieran Krishnan
That's really interesting when you think about it. Right. So lifting damages everything. We know that. Right. And then the adaptation, the repair is where we see the benefit. So in the muscles. Most people understand that lifting and doing resistance training will tear muscle fibers. You're getting the micro tears, you feel it as soreness and so on. Then you activate protein intake, creatine, all these things activates myogenic response. So then you have to rebuild the muscle, and it comes back stronger, thicker, and you can recruit more and more muscle fibers to the movement over time. So we provide ourselves that bones do well because there are these osteocytes inside the bone that sense pressure on the bone. And when you put pressure on the bone, the osteocytes lay down more mineral and bone matrix. Right? So then the osteocytes are responding to the pressure and the stresses on the bone. Now the joint is another bit of a story because the joint is taking a lot of pressure and it's taking a lot of stress as it's managing the weight that you're moving. The problem with it is that we then don't do anything specific to recover the joint. Right. We take the protein, we take the creatine, we allow the muscles to rest and so on to allow the muscles to heal. Often we'll take our calcium, vitamin D and K2 and all of these things for the bone, but we're not doing anything specific for the joint. And studies show that joint tissue takes three times longer to recover from stress than muscle tissue does. Right. And the joints are getting no repair time. It's not like we're doing all of that and then we're just sitting around for the next few weeks. So we need to become much more active in our supporting of the joint, especially if we're increasing our activity, right. And so we don't want that weightlifting and all that to accelerate degeneration of the joint. Right. Because then that'll end up being counterproductive.
- [58:33]
Dave Asprey
It's one of those things where I really truly believed that if I went to the gym six days a week, you know, 90 minutes and I just did it all, that I would improve. And I, I still regret doing that. I was only 23, I never lost a pound. I still had a 46 inch waist when I was done. And you just like eight minutes twice a week, get some recovery, support your joints. If I'd have known that, I would have been in a lot less pain and probably would have had less surgeries to too. So that's why I'm just so. I love doing the show. Because, man, if only I'd have known and have so many friends who are just dealing with joint issues, right? And you're just kind of coming along saying, well, we have this 10 year history as a company of just doing things that no one else thought about. And I've used arterosil for so long since the first clinicals came out. And you're not like supplement companies that I'm used to. You deeply medical, deeply research based. And then I used, I didn't even talk to you guys for five years after I'd been the customer, I was like, you know what, like you're doing some interesting stuff here. Like I should just share this. And then you came out with, with Vasconox and like that stuff is very noticeable. If I take a half dose for my, my biology, let's just say that the morning kickstand, the difference is profound. And I take other nitric oxide donors as well. I mean just full disclosure, I'll take an N101 tablet and I like that stuff. It's a rapid spike and I use it for specific things but it doesn't have the same long term effect. And I take the Vascanox. If I take two Vasconox which is a normal dose, it's too much for me but I think for most people they're like finally my blood pressure regulated. My blood pressure's already fine. Thank you you but man, the difference in vascular flow from vascular, it's real. And so these are things that I am a long term happy customer with before we ever not. Vasclonox, you came out with that after I met you guys. But these are things I just use and I'm so intrigued with cardiogenics and I'm just getting into using it. But your explanation that look, this does more via different pathways than the current set of drugs and stuff that people spend 200 bucks a month on. So I'm in. Anything to protect your joints. I know a few people in their 70s and 80s who did protect their joints via genetics or God or whatever and they're so happy. And the number one complaint that I hear from them is all my friends can't do anything anymore so they have to get younger friends. Right. So I would say take the stuff that Calroy makes and get younger friends now so they'll be good friends when you, you're old and you're not old because that's my plan. And Kieran. So all this is just authentic. So thank you truly for making cool stuff. And guys, you know you always save money if you are listening to the show and I talk about something that's worthy. Kalroy.com Dave and this is a stack. You can try it. Do you guys have like a money back guarantee or something? I didn't, I don't know.
- [61:38]
Kieran Krishnan
I'm sure that wouldn't be an issue at all. Yes. Yeah we will.
- [61:41]
Dave Asprey
If you don't like it, call them up. They'll take it back. Yes, there you go. I'd now guarantee I truly believe in this and God, people send me so many bottles of stuff I won't even take it's not well formulated. I just I give it away and all this and I'm not interested. So I only want to talk about the coolest, most effective things and you've been on my list for a very, very long time of stuff that I pay attention when you come out with something because you don't mess around.
- [62:11]
Kieran Krishnan
So thank you, thank you and thank you so much for this opportunity to be able to talk about it. It's such a great foundational component to people's life and health span and stacks the things that it affects. It's been really exciting to get this to come out in the marketplace and see the effect of it. So thanks for having us.
- [62:29]
Dave Asprey
See you next time on the Human Upgrade Podcast.
- [62:37]
Podcast Narrator
A Human Upgrade, formerly Bulletproof Radio, was created and is hosted by Dave Asprey. The information contained in this podcast is provided for informational purposes only and is not intended for the purposes of diagnosing, treating, curing, or preventing any disease. Before using any products referenced on the podcast, consult with your healthcare provider carefully, read all labels and heed all directions and cautions that accompany the products. Information found or received through the podcast should not be used in place of a consultation or advice from a healthcare provider. If you suspect you have a medical problem or should you have any healthcare questions, please promptly call or see your healthcare provider. This podcast, including Dave Asprey and the producers, disclaim responsibility for any possible adverse effects from the use of information contained herein. Opinions of guests are their own and this podcast does not endorse or accept responsibility for statements made by guests. This podcast does not make any representations or warranties about guest qualifications or credibility. This podcast may contain paid endorsements and advertisements for products or services. Individuals on this podcast may have a direct or indirect financial interest in products or services referred to herein. This podcast is owned by Bulletproof Media.