Dan Pardi, MS, PhD 00:00 And that it is great to see you again. I'm excited to talk about joint health. Joint health is really upstream from one of the most important health span factors that we know of, which is movement. But it's hard to move if you're really uncomfortable. So this is important in its own right, but it also then enables another extraordinarily important health span behavior. And nobody wants joint pain anyway why don't we do this? Why don't we start with a primer on joints themselves so we know what we're talking about does that sound good?
Matt O. 00:24 That's perfect.
Dan Pardi, MS, PhD 00:25 Ok, cool. Jenny and I are going to act in and talk about different parts of that and you can ask questions whenever you want. So what's a joint so there's actually lots of different types of joints in the body. We have fibrous joints this is when you have a fibrous connection between bone you have cranial sutures so imagine in your skull there's all different plates and nose have joints as those bones come together. The one that we're really interested in when we talk about joints is synovial joints. These are the ones that move and they'll be our focus for the most part. These are mobile these are your knees, your wrists, your fingers, ankles, even parts of your spine like facet joints, funny enough so I recently started the jiu jitsu and in that you grab really hard on a gi if you're doing jiu jitsu. And all the joints in my fingers, I could feel them after for like days and days on end. So you take a good healthy joint for granted until you can feel it so let's think about what the joint is so imagine these are two bones and if there was nothing protecting them, you'd experience a lot of grinding. But these bones that come together are encapsulated with a fibrous capsule. And inside that capsule there's a synovial lining and synovial fluid which is between the bones. And on the end of each bone there's articular cartilage. This is basically a built in shock absorber. It sits inside the joints and it's this smooth, thin, like a Teflon on a pan it's permanently bonded to the bone and it coats those ends. And what it does is it allows for smoother gliding even under very heavy load so it prevents that grinding and absorbs impact and cushions the joint when you're walking, you're jumping any sort of sudden movement.
Matt O. 01:51 Synovial, you said synovial.
Dan Pardi, MS, PhD 01:52 There's synovial joint that contains an articular cartilage made out of this tough collagen network that can withstand these movements for your life. This is a living structure, and it's made-up of specialized cells that are a part of this cartilage tissue called chondrocytes. And the extracellular matrix gives cartilage its unique mechanical properties it's strong but flexible, durable but also springing, and when it's healthy, these chondrocytes sense the load being placed on them, responds to the mechanical signals and then adapts. What is the extracellular matrix made-up of? It's made-up of type 2 collagen, so they go proteoglycans and elastin. Type 2 collagen provides that framework like tension cables, and it keeps the cartilage strong and tear resistant, although it can tear the part of lichens the way that I think of it is like little water balloons that are spongy molecules that retain water, absorb shock and keep the tissue springy. And then elastin, like elastic, adds stretching flexibility, but helps the joint rebound when it's stretched and moved. So together this gives the structure, the matrix, and the counter sites some unique ability to be soft enough to cushion and tough enough to withstand a lifetime of repetitive motion. One really important point when we talk about joints is that they're avascular, which means that they don't have direct blood flow to them. So if this type of tissue doesn't have its own direct blood supply, where does it get its nutrition from? The cartilage gets its nutrition from synovial fluid through diffusion. And that means that the repair process is usually pretty slow and it's also limited. In fact, damage that occurs is often times permanent. So prevention is crucial. Do you want to say a little more about synovial fluid?
Ginny Robard 03:35 Yeah, definitely. Your joints are basically high performance hinges they're bending, rotating, absorbing impact thousands of times per day. And to keep these joints moving smoothly, your body produces synovial fluid. And this is a slippery liquid that fills the joint cavity, the space between the bones so if you think like these, like 2 bones, we've got the joint capsule, the space in between the bones, and there's this slippery liquid. But the synovial fluid is a little misleading it's not like a thin watery liquid. And that's because it contains hyaluronic acid, which gives the synovial fluid it's a viscosity and shock absorbing properties and.
Matt O. 04:11 You said.
Ginny Robard 04:11 Hyaluronic acid yeah, it's a mouthful.
Matt O. 04:15 Is that IO?
Ginny Robard 04:16 It's H Y A L U R O N I C. Hyaluronic you see it a lot in skin care products because it retains water like crazy. Each hyaluronic acid molecule can bind up to a thousand times its weight in water, which makes it good for a lot of skin care products because it like it for like serums, stuff you put on your face, it makes it thicker and it does the same thing in your joints it forms like a gel like cushion inside the joint cavity. So it's a very thick fluid and this is a good thing because it helps distribute loads evenly across the joint, reducing wear on on anyone area. But the role of synovial fluid goes beyond lubrication like Dan said, cartilage is avascular. So synovial fluid is what feeds the cartilage, oxygen, glucose and amino acids via diffusion. So you could think of synovial fluid as being like WD forty for your skeleton, but honestly it's even more essential than that. And without it, cartilage would dry out, friction would build, and there would be all kinds of damage so.
Dan Pardi, MS, PhD 05:18 What we talked about so far, we have this capsule, we have the fluid inside, we have the bones, and then the cartilage is at the ends of the bones. What else does a joint have as ligaments and tendons? A ligament buffers the twisting force around two different bones.
Matt O. 05:31 Holds the bone in.
Dan Pardi, MS, PhD 05:32 Alignment it resists excess movement it allows for some but it doesn't allow for too much tendons. Think of them all like a spring they store and release energy and this is muscle to bone so this is the tendon is a part of the muscle and then it attaches the bone and it helps you transmit force so when your muscles contract and that pulls against the bone and it is the tendon that is attaching to the bone. Athletes can store and release a massive amount of energy if those tendons are strong, stiff and structurally sound. So these are made mainly from type 1 collagen like bone and skin, where cartilage is made of type 2 collagen so like cartilage, this also contains an extracellular matrix both these structures, ligaments and tendons elast into stretching, recoil and then each one of them have the equivalent of a chondrocyte. So tendons have tenocytes and then ligaments have fibre blasts. And just like articular cartilage, they don't get much blood flow and they have decreased repair rate. You need mechanical loads to remodel this tissue, which means that you have to use them. Diffusion is how they get their nutrients. So use the ports. In terms of ligaments, tendons, and cartilage, they actually have a very good response to training, but at the same time, they can be injury prone. That's our primer on this. And why don't we talk about the landscape of joint problems in the United States do you want to take this one?
Ginny Robard 06:53 Yeah, sure thing. So Matt, I'm sure won't surprise you to hear joint issues effects a large portion of the adult population in the US and they're actually a lot of different types of joint problems like tendinopathies, Bursitis, labral tears, meniscal injuries, ligament sprains. Dan was joking earlier that he he just about has all of these so we could probably put a picture of Dan's body like outline, make him like the silhouette and just label it.
Matt O. 07:21 Yeah, I was talking to the surgeon that did stem cells on both of her boys and he was saying if I took Mris of a thousand said nine hundred and ninety of them would have multiple tears in their labrum that rotator cuffs like the he said they are there all the time in general and some people have different relationships with them, right some are debilitating and some when you look at the image look debilitating and they have 0 effect on their pain at all like they can't even they don't even know they're there.
Dan Pardi, MS, PhD 07:58 There's a lot of different types of issues that happen with the joints, right there's pheninopathies, Bursitis, and that's just from playing sports hard, grown up, always being active. If you've been an athlete, even if you haven't been, it's likely that some or all of these things are things you can personally relate with. And yeah, and as you get older, you have more time to aggregate the chance of causing injury. In fact, arthritis is the most common, most recognized, it's the best studied, but it's actually not a single disease how many different conditions Jenny considered as a part of arthritis?
Ginny Robard 08:31 Arthritis is an umbrella term for actually 100 different conditions that affect the joints.
Matt O. 08:35 Yeah, wild. That's crazy. And how many?
Dan Pardi, MS, PhD 08:39 People have experienced this in the United States they're adults.
Ginny Robard 08:44 That's a complicated question if you look at everyone 18 plus, the latest CDC data says 20 % of adults but if you break it down by age, it looks different. It's really when you're talking about it's really low up to when you're in your thirties thirty, five to 49 it's 12 %, then age 50 to 64 - 29 %, then 65 to 74 it's 44 % and in people over the age of 75 it's more than half of the population.
Dan Pardi, MS, PhD 09:11 Yeah, right half of the population have joint issues by a certain age. Yeah, that's some people. This is.
Matt O. 09:17 Sporting, right, Kenny that's reported stuff.
Dan Pardi, MS, PhD 09:20 Right this is diagnosed arthritis actually. So think about that. If 50 % of the people have diagnosed arthritis, what about that large group of people that are dealing with some sort of joint issue arthritic like condition just hasn't been diagnosed yet so this is or this is.
Matt O. 09:35 Something you don't get.
Dan Pardi, MS, PhD 09:36 Yeah, it's a lot of people.
Matt O. 09:38 It's a yet to be discovered thing that we have no idea about.
Dan Pardi, MS, PhD 09:40 Yeah, You also have that people that haven't gotten to the doctor, they're experiencing it they just haven't gotten an official diagnosis. All right, What happens, What goes wrong over time? And like a lot of things in the body, joint decline is gradual and so it's often unnoticed only until the person has pain and discomfort. And there's basically at that point enough structural damage present for it to be causing some issues that you can perceive. And the different drivers are things like repetitive stress, so daily use to intense sports, unhealed injuries, so injuries that you didn't get complete resolution on when you were younger or at some point and they've stuck around. And then of course, aging, right so the three main processes of deterioration with age is you do have structural breakdown so even if you don't have some big injury, you do experience structural breakdown. So you see less production of type 2 collagen and elastin, the stretchy stuff. And then the extracellular matrix weakens too so you now have increased surface roughness, which causes more friction, causes more wear. You can't handle loads as well. And so now you're in a situation where you're also going to accelerate the structural damage because the loss of the protective layers between it so it's, it's not a linear curve, it's actually one where you see the situation get worse at an accelerating rate. You have less lubrication and less nutrient delivery so the synovial fluid decreases you have less hyaluronic acid, that synovial fluid think of it like a gel that thins out it goes from a thicker gel to a thinner gel. It's less cushioning, less lubrication, less nutrition, right because remember, where do these structures get their nutrition from the synovial fluid? And then that gives the feeling of dry, stiff, damage prone tissue so you wake up in the morning and you feel stiff and achy until you warm up, right and your feet are sore, your knees are sore, whatever it is, wherever you have more damage, you feel that first and then with a little bit of movement, it can loosen up and I'm sure that can relate to that. Get older. Yeah, Yeah, it's a still like a normal characteristic of getting there and then of course, like anything with aging is chronic inflammation. So as inflammation is a double edged sword, right? And we tend to try to label things that occur in the body as bad inflammation, bad that's not true. If it's acute and short lived, it's helpful we want inflammation because it recruits immune cells, it clears out the debris and it kicks off healing it's a part of that healing process when you do have little micro damage. But what we really are worried about or concerned about is chronic low grade inflammation because that persistent inflammation erodes the joint tissue from within. It's a situation that is toxic to the tissue. What we're really trying to do is restore inflammatory homeostasis for balance because it does play an important role in maintaining the tissue in fact, that's one of the issues is that when you end up in a place with chronic inflammation, the function of normal, healthy inflammation becomes deteriorated. And that's no good no, we don't want to shut down all information, but we do want to get out of that chronic inflammation state. So what happens to joints under chronic inflammation why is it bad?
Ginny Robard 12:34 Yeah so we used to think about joint degeneration, like osteoarthritis as being a simple sort of wear and tear problem. But we now know that's actually only part of the story. New research shows that inflammation plays a central role even in the earliest stages of joint breakdown and the reason why we know this is because researchers have looked at synovial biopsies from people with various stages of osteoarthritis so some people only have a tiny little bit, and other people like they're about to get a joint replacement. And these biopsies consistently show elevated levels of inflammatory cytokines even in people who are at the very earliest stages. So these inflammatory markers are present before there's major structural damage apparent, which suggests that inflammation is not just responding to joint damage, it may actively drive it. Ongoing mechanical stress as well as cellular aging tip the system to chronic inflammation so immune cells get activated in the joint and they release various pro inflammatory cytokines. So these are small molecules that signal inflammation. But the problem is that these cytokines don't just increase inflammation, they also as molecular signals that bind to receptors on other joint cells. They bind to chondrocytes as well as synovial cells, and these cells shift to a catabolic state, meaning that they start breaking down the extracellular matrix instead of building and maintaining it. And more specifically, they start ramping up production of various what I would call breakdown enzymes and this includes matrix metalloproteinases which degrade collagen, and agriconases which breakdown agrican and Agrican is the main water retaining molecule in cartilage. So these enzymes aren't inherently bad you actually you need them to remodel damaged tissue but the problem is when they're active all the time, you start seeing accelerated collagen loss, thinning and weakened cartilage, and overall breakdown is outpacing the body's ability to repair. So this creates A destructive loop where immune cells are releasing cytokines, the chondrocytes respond by producing these breakdown enzymes cartilage starts breaking down, releasing debris and then in response more inflammation is triggered. So this propels joint degeneration even in the absence of recent injury. And importantly, these cytokines also trigger another inflammatory pathway, cyclooxygenases, which are better known as Cox enzymes. Matt, are you familiar with Cox enzymes by any chance?
Matt O. 14:59 I am not i'm taking that sorry. No, I'm not.
Ginny Robard 15:02 Yeah, they might start ringing a bell as we talk about them. So Cox enzymes make prostaglandins, which there's like local hormones that act over a short distance and there are two different types. One is Cox 1 Cox, one is always turned on. It maintains protective prostaglandins and the lining of your stomach. Cox 2 is only switched on by injury, inflammation or infection and it drives pain and inflammation and too much Cox 2 leads to joint damage so what do people usually do when they have joint pain they take incense non steroidal anti-inflammatory drugs like ibuprofen, naproxen these drugs work because they block Cox 2 which is great because it it blocks pain and blocks inflammation the problem is that it may also block Cox One, which produces GI side effects, and that's because Cox One protects the lining of your stomach. The prostaglandins in your stomach promote mucus production bicarbonate, which neutralizes stomach acid and also promotes healthy blood flow to the gut. So blocking Cox One disrupts this defense, leading to ulcerous GI bleeding that's why if you take ibuprofen or Aleve too much, you're obviously going to feel less pain and less inflammation, but you also will wind up with problems with your stomach. You can develop ulcers and GI bleeding and this is a problem that pharmaceutical companies have been dying to solve for decades and actually almost did with Vioxx do you remember Vioxx about 20 years ago? Yeah dan, do you want to explain Vioxx a little bit?
Dan Pardi, MS, PhD 16:35 So I have selectively inhibited Cox-2, which is great, right Cox-2 is going to drive joint inflammation you get an up regulation of Cox-2 when you've got pain and swelling. And so inhibiting that people would feel immediate relief. And as a result, it became a blockbuster drug, two billion dollars in sales. You weren't affecting your gut lining like the NSAID's and Naproxen. So this seemed to be a great thing. What ended up happening is that being on these medications for a long period of time doubled cardiovascular events and there was a trial called the approved trial that showed that you were on it. You were more than twice as likely to experience some sort of cardiovascular event, like a hard second yeah so Merck ended up withdrawing this in September of 2004 And even though they need over two billion dollars they had massive litigation and so the lawsuits were closer to five billion dollars of payouts. And there was thinking that they sat on this information for too long. Like they knew that there was a signal there, but they didn't want to remove it because the drug was doing so well and that right? But there's the, if the incentive is strong enough, they're not going to take this off the market even when they should. And now pharmaceutical companies are much better about that if there is a signal, they might remove from the market, do more research, even if they end up putting it back on. But this was not a good look for Merck. And it definitely was one of the Seminole moments in the pharmaceutical industry's reputation. Some key points there is that, yes, excessive Cox-2 causes joint damage. We don't want that. But Cox-2 is helpful when controlled. So we're not trying to eliminate it, but we are trying to keep it in check. And I came up with this acronym curve, which is calm, inhibit, reduce and preserve. So you're trying to calm Cox-2 and your pro inflammatory signals down inhibit certain enzymes so genius mentioning a matrix metalloproteinases. These are these enzymes that can break down the structure really important to clear out debris and then reduce swelling, stiffness and pain we want to get rid of that that's that is our physical experience of what's happening inside the body and then preserve long term structure and Tonkin as long as we can so calm, inhibit, reduce and preserve so cool the fire without getting rid of the firefighters. Got it. I do want to mention the one thing about cortisone shots so Ginny said what happens when you develop brain pain you might take up non steroidal anti-inflammatory drugs. Another thing that people do if it's bad enough and the NSAID's aren't working is they'll go get a cortisone shot. And what recent research has shown is that this actually worsens the condition overtime yeah.
Matt O. 18:55 And is that connected to somehow like creating a situation where Cox-2 enzymes then come back?
Dan Pardi, MS, PhD 19:02 What you're doing with a cortisone shot is you are getting temporary relief by suppressing pain signals, but you are breaking down the tissue further. There was 2 studies that support this ID, but the corticosteroid shots worsened the condition. One of them was a 210 person study that used magnetic resonance imaging, MRI and showed that the disease progression was accelerated over time when you have these shots the second one has 150 patients in it and it was a radio graphic study that also confirmed worse outcomes over time too. So what's better is getting injected with either onic acid, right, That gel like substance that seems safer and it also has been shown to decrease disease progression. I would rather opt for that i would rather slow down the deterioration then feel better for a little bit and accelerate the deterioration because you're basically just pushing off the issue downstream yeah all right. The aging problem, all right we talked about the various things that happen when you do age there's breakdown in structures, there's inflammation. There's a variety of those things that we talked about. There's other things that take place though. The cells, the cognocytes, tenocytes, etcetera, they become less metabolically active when you get old and they're more prone to senescence. And as you are aware with senescence, you have cells that are not functioning or they're releasing more inflammation into the immediate area now typically. The release of what are called SAS factors, it's over 120 different inflammatory molecules that plays a physiological role. It signals to the immune system, hey, there's an issue here, Immune system come clean up this damage. But as you get older, you have more senescent cells and weakened immune system, so no longer as helpful with a situation as before. And they're also less responsive to mechanical stress so before how do we keep these tissues healthy we have to use them, right because they get their nutrition through diffusion, but they're now less responsive to that. A good example actually to understand this is skin. A very similar process is taking place in skin, though skin fibroblasts also manufacture collagen. And with age, this lower metabolism that increase in essence decrease collagen production. And you see this as visible evidence in wrinkles. And you the same exact process is happening in your joints you can't see it, but you can feel it, right? We've covered what a joint is we've covered what happens with aging we understand how these tissues work through their limitations and their capabilities. We see how certain common drugs like NSAID's Orgasteron shots are not as helpful as you'd want. So now it asks the question, what does help? Let's talk about the movement side first, so we can understand what's helpful so that we can design programs for your movement mat that include this stuff that's going to help.
Ginny Robard 21:32 Yeah, inactivity causes collagen production to decline or stagnate but the good news is that tendons, just like muscles, are highly responsive to mechanical loading. Exercise itself stimulates collagen synthesis to a surprising degree. Even 1 resistance session can double the rate of collagen synthesis. And over time, this results in stronger tendons there was one study in older adults, we're talking like 70 to 80 years old. Fourteen weeks of strength training led to a 70 % increase in tendon stiffness. Remember, stiff tendons are good. They transmit force separate.
Matt O. 22:10 Separate from joint stiffness bad.
Ginny Robard 22:12 Yeah, yeah, tendon stiffness is good. I know it's counterintuitive, but yeah, tendons.
Dan Pardi, MS, PhD 22:16 Difference, I remember it. So what happens to skin also uses collagen when you get older. It becomes saggy, it becomes less stiff, it becomes more relaxed tendons are like that too. In fact, they're about 15 % more compliant than younger ones so they deform more under load and they have a decreased ability to transmit that for so less stiffness is like saggy skin. Resistance training actually helps to keep your and stiff and that helps with force transfer so that's.
Matt O. 22:44 Good resistance training means lifting weights, using bands, running, walking. Is that true or is it more lifting weights and?
Ginny Robard 22:53 Yeah, for most people walking and probably running, unless you're like sprinting, is not going to be enough of a stimulus for like most healthy individuals.
Matt O. 23:01 And lifting weights using bands.
Dan Pardi, MS, PhD 23:04 Body weight.
Matt O. 23:05 Maybe could swimming do that or no is it not weight bearing so it doesn't really have the same effect or it's.
Dan Pardi, MS, PhD 23:10 Going to be more modest putting stress on the tendon so like body weight will do it. Lifting a load certainly will you're going to get a modest amount to bat with swimming if you're working hard through the water and the muscle is now going to be contracting and pulling the tendon.
Matt O. 23:26 Of the Yeah, because you're it's on the.
Dan Pardi, MS, PhD 23:27 Folding yeah, exactly.
Matt O. 23:29 Or if you're forcing your leg down through the water, it might be resistance a little bit but what you're really talking about is body weight like push ups, lunges, squats, step UPS, pull ups and all weight lifting and maybe band like band work like pulling resist training, band work I had so my here's my question for you so we're talking about loading up tendons. Is the same thing true for ligament and cartilage?
Dan Pardi, MS, PhD 23:57 Yes, because the loads are going to facilitate better diffusion of nutrients and oxygen into those particular tissues because just using them.
Matt O. 24:08 Avacular, right? The reason why usage is good is because like just talking about like the synovial joints, you have to get the nutrients into the synovial joints and then by process of osmosis it gets into the cartilage, right? What is actually going on when you load it up that helps that process happen faster?
Dan Pardi, MS, PhD 24:28 Think of these tissues like a sludge. Right when they're in use, the sponginess of these tissues is going to increase and you're going to get better exchange of extracellular fluid inside of those particular tissues that gets more spongy with usage.
Ginny Robard 24:45 When it's under tension.
Dan Pardi, MS, PhD 24:46 Yes.
Ginny Robard 24:47 So if it's getting, if it's getting.
Matt O. 24:49 If it's getting, if it's a synovial joint, it's getting pounded, it's going like that so it's getting moved around if it's a pendant, if it's like your hip flexor, boom, I'm lifting my leg up, I'm stretching this out and I'm using it. If it's a ligament, then some sort of analogy there but basically if it's being moved, it turns into more spongy because it because it's being moved, it's like a it's if you took a dry sponge, it's brittle, but you pour water on it, it's a little bit more spongy and it can take more water.
Dan Pardi, MS, PhD 25:18 That's right, Yes, it can get.
Matt O. 25:19 More of it can get into the cartilage through the synovial fluid if it's being used because it's spongier, it's able to bring in more and more.
Dan Pardi, MS, PhD 25:27 Ok. The synovial fluid is only going to be in that synovial joint capsule. It's not affecting the tendons or the ligaments, But very similarly, diffusion is what's going to help all of those tissues get their nutrients that's the main idea I saw. I did a podcast with Keith Barr, researcher at UC Davis, and he showed that by taking collagen 45 minutes before training, you see increase in collagenation of tendons over a training period. That requires some vitamin C as well. But if you consume hydrolyze collagen and you before you go exercise, then it's going to be present while you're then making the tissues more spongy. If there's no nutrients, you're not really helping that much but if you are loaded up with collagen and that collagen is now getting into the tissues, those spongy tissues, that's one way in which the supplemental hydrolyzed collagen peptides are going to help keep those particular tissues healthier. Got it. So actually, let's talk about collagen. There's a lot of different types. There's at least 28 different types of collagen in the body. And when it comes to joints, a few types do the heavy lifting so Jenny, do you want to talk about type one two and three?
Ginny Robard 26:39 Absolutely, yeah. So type 1 is found in tendons like a man's bone and skin, and has a high tensile strength. Type 3 is found in skin, blood vessels and connective tissue, and it adds elasticity and support. So types one and three are found in hydrolyzed collagen like that's the typical collagen supplement that you see in the tubs. There's another type, type 2, which is found in articular cartilage. Its main function is shock absorption and load distribution and this is not in most hydrolyzed collagen. So we will have to come back to that one later that's a little bit of a special case, but what we're talking about right now with hydrolyzed collagen peptides, that's types one and three, and they are ideal for supporting tendons and ligaments. And the way they work is actually interesting. So most people think that taking collagen is directly providing building blocks for your joints they're like delivering bricks to a construction site but that's not, and that's, it's true you do need the amino acid building blocks, but that's not the primary mechanism. Actually, when you're supplying types one and three, it's more like pulling an alarm to mobilize a repair crew. In other words, hydrolyzed collagen acts more like a signal. And in order to understand this you need to think about what happens when tendons are put under stress. They start to break down and they release these collagen derived dipeptides, meaning pairs of peptides that are bound together like proline and hydroxyproline or hydroproline and glycine. And these pairs of peptides basically serve as a signal to the body that it's time to repair. So when you are supplementing with hydrolyzed collagen peptides, you are mimicking this process you're flooding the bloodstream with the same peptides that are released after tissue stress, which kind of tricks the body into prioritizing collagen synthesis and repair. And when it's repaired, when you pair this with resistance training, this molecular mimicry can accelerate and amplify the body's own tendon remodeling response so it's pretty cool actually.
Matt O. 28:37 Ok, so type one and three, basically by supplying hydrolyzed collagen, it sends a signal to your body and the collagen derived dipeptides are released and the body says it's time for me to now repair. And so if you give these peptides to your body, then it tricks your body into starting the remodeling response. Ok, I got to start fixing something and I'm going to look at tendons, ligaments, bones, skin, blood vessels, depending on what the type is that's what I'm signaling does.
Dan Pardi, MS, PhD 29:08 Exercise supports skin collagenation through the mechanism that we're talking about. So there is a little bit of damage from the use of the tendons or if the dypeptides trigger the rebuilding response and is collagen throughout the body then remodeled and I wouldn't be surprised if the answer is yes, but I would also not be surprised if there is because of the damage there's an acceleration that occurs at the areas that we're releasing the dypeptides in the 1st place through use.
Ginny Robard 29:36 So I think the specificity is important and that's suggested by the fact that resistance training seems to be you pairing this with resistance training seems to be important. So it seems like applying stress is a key stimulus combining with the collagen, at least with the trails that we've looked at. Ok, so.
Matt O. 29:53 Sorry to just repeat what you just said because I wanted to make sure I got that. So what you were just saying was actually you need to be like very specific when you're talking about this, right so when you're taking type one and three, the trials stated by supplying the hydrolyzed collagen and doing the risk resistance training, those two together send a signal to your body and then the collagen derived dipeptides are released and the signaling to the body that's time to repair and then the peptides in your body tricks your body into remodeling is that.
Dan Pardi, MS, PhD 30:25 There's a little nuance there. Sorry, Jenny, I don't mean to cut you off no go.
Ginny Robard 30:28 Ahead.
Dan Pardi, MS, PhD 30:29 I think it's actually important i don't mean to be.
Matt O. 30:31 No, I want to get a specific.
Dan Pardi, MS, PhD 30:32 I want to get it yeah yeah, it's fine think of it this way training releases the dipeptides normally. Ok. Supplemental hydrolyzed collagen mimics that process, but exercise with peptides does have evidence for it being particularly useful. There was a study that was looking at Achilles tendon thickness it was 14 weeks it was young people around 26 average in the study, five grams daily greater than two time increase in Achilles tendon dies. There was twice the growth in the Achilles tendon by taking 5 grams a day over 14 weeks. That's awesome. And that essentially has been replicated in other ways looking at patellar tendon stiffness. This was a study that was in 2023 Also young people, elite female soccer players, oh, 17 years old, even younger, 10 weeks, 30 grams of collagen with some vitamin C you'll see that vitamin C is often taken its part. It's necessary to have on board for the metabolic benefit of the anabolic process that takes the collagen and helps make the tissue. This was only taken three times a week, and this was taken post workout. That's everything so we take it before and take it after. This was taken post workout. In this case, there was a three times greater increase in tendon stiffness. So the last study I was mentioning about Achilles tendon, there was over twice the growth and in this case there's over three times the stiffness. So we're seeing anatomical changes we're also seeing functional changes that you want to see, right?
Matt O. 31:57 So it has to be paired with vitamin C.
Dan Pardi, MS, PhD 31:59 Yes, you'll notice that most supplements now include some amount of vitamin C in the formulation of your vitamin C. See, status is good and you're eating a healthy diet you don't have to take it supplementally, but a lot of supplements do include that because the Co consumption of those two is as direct research behind it as being beneficial.
Matt O. 32:18 Got it.
Ginny Robard 32:18 Yeah, Vitamin C is important for is it an important Co factor for collagen synthesis that's why in people with scurvy, some of the earliest symptoms of scurvy, which is severe vitamin C deficiency, is that they'll have bleeding gums and they'll have joint issues. That's the earliest sign that you've got a serious problem, simply because vitamin C is so critical for collagen.
Dan Pardi, MS, PhD 32:40 Wow, Jenny, how much do we need?
Ginny Robard 32:43 How much do we need?
Dan Pardi, MS, PhD 32:43 1-1 siding was 5 grams a day, the other was 30 both had an effect.
Ginny Robard 32:47 Oh, collagen you mean? Yeah, Sorry, I thought you were asking about vitamin CI. Don't know the RDI off the top of my head. Yeah, so you're touching on an important point here there have been a ton of studies that have tested collagen peptides and it's hard to interpret because they use a really wide range of doses. So it's the question is how much do we need specifically for promoting these tendon adaptations i think. And so one very recent short term dose response study where they basically they take these resistance treatment and they give them different doses as well as placebo, meaning like 0 grams they found that 30 grams of collagen boosted collagen synthesis beyond the effects of exercise alone, because exercise by itself also boosts collagen synthesis. And they found that 15 grams, which was the next highest dose had the same effect as placebo in other words, it didn't work at all. So they concluded that specifically for spurring these tendon adaptations that that we're talking about here, 30 grams is the minimum effective dose for stimulating collagen synthesis and that actually mirrors that soccer study that Dan was talking about where the teenage soccer players, they were taking 30 grams of collagen and vitamin C after after training only after training three times per week.
Matt O. 33:59 They were taking 30 grams of collagen and how much vitamin C i'm sorry.
Ginny Robard 34:03 I don't remember the exact dose of.
Dan Pardi, MS, PhD 34:04 Vitamin D seventy five milligrams. Yeah, it really.
Ginny Robard 34:06 Doesn't take that much honestly. Most people really don't need to worry about it at all if you're eating like fresh food, 'cause if you're eating like fresh fruits and vegetables, you really don't need to worry about it that much.
Dan Pardi, MS, PhD 34:17 Ok i was off in order to mention it was 500 milligrams of vitamin C, not 50.
Ginny Robard 34:22 Yeah, you don't need that.
Dan Pardi, MS, PhD 34:22 Much but that's a lot, actually.
Ginny Robard 34:24 I actually wouldn't then taking that much.
Dan Pardi, MS, PhD 34:26 I agree you might be blunting some of the signals that lead to adaptation so a smaller amount, probably 50 milligrams usually would be adequate that's what Keith Bar use, 50 to 75 milligrams, 500 is a lot and that might be too much.
Matt O. 34:38 They, so it's interesting, they took 30 milligrams of collagen grams, sorry, 30 grams of collagen along with say 50 to 75 milligrams of vitamin C. And did they take it all in one dose or did they split it up like what can your body take in terms of collagen?
Dan Pardi, MS, PhD 34:58 Yeah, that's a good question.
Ginny Robard 34:59 Yeah, they took it in one fell swoop.
Dan Pardi, MS, PhD 35:01 The study that I mentioned earlier with the podcast with Keith Barr, they took it 45 minutes before training and the idea was get into your circulation while these sponges are being used. In this case it was taken afterwards, but it is possible and I don't know how long the altered sponginess of these tissues is going to occur after exercise, but I think without that knowledge immediately present in my mind or it might even be known there is some biological possibility around taking it 45 minutes before or right away after.
Matt O. 35:33 If you took it right before and then you worked out for say an hour and a half, I would think that it's still diffusing through your bloodstream like from that 45 say an hour before a hour, it's got to be in your bloodstream for at least like 3-4-5 hours.
Dan Pardi, MS, PhD 35:49 It's going to diffuse into the tissues, but if you want to play around with what if you did 15 grams before and fifteen grams immediately, after just to, from a practical perspective, reduce the load of collagen that you're taking, I have no reason to believe that wouldn't be useful.
Matt O. 36:05 Yeah.
Ginny Robard 36:06 So I'd like to talk. We're talking about timing the study that I was just about to describe, they took it immediately post training the 30 grams of hydrolyzed collagen and the effects were pretty impressive. So the previous study established that 30 grams is the minimum effective dose for stimulating collagen synthesis in this specific context. What does?
Matt O. 36:27 Immediately post training mean like within 30 minutes.
Ginny Robard 36:30 Yeah, probably. But the question is that's the previous study was looking at short term effectively biomarkers of collagen synthesis like surrogate markers but the question is, does that translate to long term tendon remodeling and does it work in aging tendons? So there was a new trial that was published this year, like a couple months ago, and the researchers recruited 20 men aged 40 to 60 and put them through 12 weeks of progressive resistance training just twice per week. So twice per week, right after working out, the men took 30 grams of hydrolyzed collagen plus 50 milligrams of vitamin C so as you'd expect, both groups gained a similar muscle size and strength but what did happen is collagen enhanced tendon thickness almost 6 fold and tendon stiffness about threefold compared to placebo and.
Matt O. 37:24 With the, I'm sorry, OK, go ahead, finish that and then I'm going to ask for clarification on doses yeah.
Ginny Robard 37:29 And one thing that's important is the growth was concentrated at the attachment sites, which.
Matt O. 37:35 Which is important.
Ginny Robard 37:36 Of the tendons, which is important because attachment sites endure the most stress during movement and that's commonly where you see tendinopathy.
Matt O. 37:44 Thickness and you said how much tensile strength?
Ginny Robard 37:48 I said that the tendon thickness increased almost 6 fold compared to placebo.
Matt O. 37:53 Ok. And you didn't say anything about like?
Ginny Robard 37:55 You do see a little bit of increase with placebo simply because resistance training itself boosts tendon thickness and stiffness because your tendons respond to mechanical stress.
Matt O. 38:05 And what was the timing on that again, it was 45 minutes before or immediately post training.
Ginny Robard 38:10 Immediately post training.
Dan Pardi, MS, PhD 38:11 Ok. A minute ago I was talking about the study in the young people, the Achilles tendon, 5 grams a day for 14 weeks. So that doubled in terms of compared to placebo. This is 30 grams, not 5. And you see close to a six fold improvement over placebo in terms of thickness and at least in terms of the growth now different studies, different populations, but what it shows to me is that there was more benefit to be had with a higher dose. The study that used 5 grams probably wasn't using enough to maximize the benefits.
Matt O. 38:41 Yeah, one of our children was instructed to take 50 grams daily in two different, three different doses, Two different doses throughout the day. Recovery from tendon. So interesting yeah, yeah.
Ginny Robard 38:54 Yeah, like, on the one hand it sounds crazy taking 30 grams, but when you consider that in this study they were only taking it twice per week, that's actually not that crazy like 60 gram 60 grams per week of collagen is not that insane of a dose honestly.
Dan Pardi, MS, PhD 39:08 Yeah, it's crazy i wanted to mention something. There's actually something pretty interesting about REST. So we're talking about hairy activity right right before, right after. But there's some interesting stuff about Ologen that you should know about. Connective tissue turns over all the time. So repair is going on even when you're not treating. And so there's a study that basically showed that 5 grams of hydrolyzed collagen, This was also done by Keith Barr, who I mentioned earlier, but I don't want to confuse things that study, it was a different study, but he studies this a lot. And 5 grams of hydrolyzed collagen supports this ongoing repair process of connective tissue. And that's especially useful for maintenance, recovery, deloading periods. And that supports this rationale that if you combined frequent small doses within a larger doser around training so like you have a daily five gram dose, which is easy to add to your coffee, we can talk about practically how to do something like this. Then in addition to that, you have some either before or after your training and you're going to have optimal benefit in terms of type 1 collagen affecting the tissues that particular type of collagen effects.
Matt O. 40:12 Can we talk about type 2?
Dan Pardi, MS, PhD 40:14 Yeah, go ahead, Jen.
Ginny Robard 40:15 Yeah let me just quickly recap what we're talking about we're talking about a dual dosing strategy for collagen the idea is that you are taking 5 grams of hydrolymplized collagen daily as a sort of maintenance dose, which supports baseline connective tissue repair and remodeling even on rest days. And then you would take maybe two or three targeted mega doses around training, which would be 30 grams of hydrolyzed collagen, ideally taken within one hour of resistance training and it's not clear if it's important, if it's before or after. I think just whatever is convenient. But yeah, UC 2 is really different. Just to recap, hydrolyzed collagen peptides, types one and three stimulate your body's natural collagen production they mimic repair signals released during tissue breakdown. Undenatured type 2 collagen works totally differently. It's not hydrolyzed, it's not broken down into peptides it is a structurally intact protein fragment that sends a message not to your joint tissue, but to your immune system. So oddly enough, there's so many diseases where the origin basically is your immune system making a mistake, and osteoarthritis is no exception. In osteoarthritis, one of the problems is that your immune system misidentifies cartilage as a threat, and this triggers chronic inflammation and progressive tissue breakdown. C2 basically acts as a reverse vaccine. It trains the immune system to stop overreacting to type 2 collagen in your joints. This is a process known as oral tolerance, and it's actually how your body normally prevents overactive immune responses to harmless proteins. Yeah, this is a very normal process through which your immune system is trained. So the idea is that undenatured type 2 collagen does not suppress your immune system, it educates it.
Matt O. 42:02 So the Horbaach Multi-Collagen protein, it has 1-2-3-5 and 10 yeah. Is the type 2 in that one two three five ten OK to take for?
Ginny Robard 42:14 It's OK to take, but it won't work the way that we're describing because it's been broken down into into.
Matt O. 42:21 It won't work to help your it won't work.
Ginny Robard 42:24 They won't have a special effect to protect cartilage by modulating your immune system, or it shouldn't, but the good news is you don't need very much.
Matt O. 42:32 How do you get that structurally intact fragment?
Ginny Robard 42:36 If you look at your Qualia joint health, it contains 66 milligrams.
Dan Pardi, MS, PhD 42:41 Of it, yeah, yeah.
Matt O. 42:43 It's milligrams of type 2.
Ginny Robard 42:47 It should be listed as UC two under the the ovemet so.
Matt O. 42:50 Ovemet. Ok. Egg shell membrane. Ok. Uc denatured collagen, 66 milligrams that's right yeah. And then it has hyaluronic acid, 9 milligrams yeah OK. And then. Ok cool all right. Got it so that's what supports cartilage health, I should say.
Dan Pardi, MS, PhD 43:09 What is it doing to support cartilage health?
Matt O. 43:12 Is this an open book can I open booklet?
Ginny Robard 43:14 We will look at you.
Matt O. 43:15 All right, so I'm looking back at my notes here. All right, let's see and I'll try and do this quickly so that you can just give me the answer so I don't.
Dan Pardi, MS, PhD 43:23 For everybody but.
Matt O. 43:24 So the hyaluronic acid in the synovial fluid can retain about a thousand times of its weight and water, it's like a thick gel like fluid. So it helps reduce load across the joint and bio diffusion occurs inside that fluid. So the type 2, if you have hyaluronic acid, at least that's what's helping one aspect, yeah.
Dan Pardi, MS, PhD 43:48 That's right, yeah.
Matt O. 43:49 The undenatured collagen, again, we didn't talk about it much we were talking about one in three collagen types, but under nature, 2 is found in. It's good for cartilage somehow i don't really know why.
Dan Pardi, MS, PhD 44:02 It's telling the immune system don't attack me.
Matt O. 44:05 Ok so under nature 2 says hey immune system leave me alone.
Dan Pardi, MS, PhD 44:10 Yeah, Yep. So getting out a really nice analogy says you have like a reverse vaccine so a vaccine is something that you put in your body that's got a fragment of the outer membrane of a virus and then it says, oh, recognize this immune system, attack this when you see it again. So if you get if you get a vaccination, if you get exposed to the actual pathogenic virus, then the body knows how to attack it. This is the opposite.
Matt O. 44:31 He goes in there and it says, hey, by the way, don't send a lot of things like the Cox 2 enzyme.
Dan Pardi, MS, PhD 44:40 I wouldn't put it that way, but I would say immune system. This tissue's OK, It's not foreign, don't attack it. And because these tissues are a part of our body, we don't want the immune system attacking it. And because when it does, it breaks it down and then.
Matt O. 44:56 That's finding, that's what we're finding with joint health over long periods of time. It's one of the but one of the reasons why we have stiffness, why we have joint issues and pain and what not over time is because they are worn down over time by the body either attacking or usage. It's one of the reasons.
Dan Pardi, MS, PhD 45:14 Why it's exactly that's the best way to think of it. It's not the reason, it's one of the reasons. Ok, so.
Matt O. 45:19 Undenatured collagen way different than way different than hydrolyzed is that what you?
Dan Pardi, MS, PhD 45:25 Said hydrolyzed type so.
Matt O. 45:26 Type 1 type.
Dan Pardi, MS, PhD 45:27 One and three type 2 quite different.
Matt O. 45:30 So the hydrolyzed 1 and 3 is much different than the undenatured 2.
Dan Pardi, MS, PhD 45:37 Yeah, and some research supports this so even just 40 milligrams a day of the ugly natured type 2 decreased joint pain, decreased stiffness, improved mobility and walking distance. And in fact, it actually outperforms glucosamine and chondroitin in head to head trials.
Matt O. 45:52 In addition or no?
Ginny Robard 45:54 It's not bad, but glucosamine chondroitin is no longer considered to be the best supplement. I don't think it's actively harmful, but it's been left in the dust by the substances that we're covering here.
Matt O. 46:06 By the undernatured collagen and the hydrolonic acid.
Dan Pardi, MS, PhD 46:09 And some other ones too. So can.
Matt O. 46:11 We talk about the other things that are on there or no?
Dan Pardi, MS, PhD 46:13 I definitely, but I want to make a really important point here all those benefits that I just mentioned, decreased joint pain, decreased stiffness, improved mobility, all the stuff you want. It takes time. You see objective results in about 3 months. It's not something you take and have immediate benefit. These tissues take time to remodel that requires knowledge and patients if your expectation is I took it for a week, I didn't feel anything, you might have given up something that significantly would improve your quality of life in terms of your mobility and your joint health. Don't give up too soon set expectations that at least some of these compounds that we're talking about, they take a little while to show up. And you know what? You acclimate to that feeling. You might, for you might experience real benefit and forget where you came from. Once the problem is on, here I go, I'm good. And you stop taking it, and then the problem goes back. So what you want to do is understand the science, understand the time frames, and then if you believe in it and you want to support your system in that way, you stick with it in perpetuity. Yeah, exactly.
Matt O. 47:13 Can we talk about the other? Let's see on this label and what they do.
Dan Pardi, MS, PhD 47:17 So we talked about egg shell membrane and that's a really interesting one it does contain these under natured type 2 collagen peptides and there's three things that are a part of it that make it special. So it has hyaluronic acid. We talked about that as being important to keep that gel between your synovial joints thicker, better shock absorption, healthier, better nutrient delivery so that's all good, right? Corpus steroids out. Getting hyaluronic acid injected into your joints actually is better and decreases the disease process. Awesome eggshell membrane has hyaluronic acid. It has some droitin sulfate, which is one of the things that we're talking about as the most commonly used for joint health there's some benefit there. And then it has this under natured type 2 collagen it's got three things that we are really interested in for joint health they do different things that are complementary and what does study do the droitin helps by inhibiting asthmatic breakdown? It has shown a decreased pain and improved mobility. So that's good, particularly around like the knees and the hands. Some studies show that it can actually decrease the joint space narrowing so that's like a double negative. It prevents the reduction of joint space by taking conjoint. So it actually keeping the distance, that's good. But the effect, the effects are pretty slow like we were talking about, but they're more durable. And with undenitured type 2 collagen, this is going to be something that's going to take a while for it to work. So what are the three things that eggshell membrane has that we care about there's three ingredients that we care about that are useful.
Matt O. 48:40 Ok. What I heard you guys say is that the three ingredients are undenatured collagen , hydrolonic acid and then control and then control it and.
Dan Pardi, MS, PhD 48:50 Sulfate nailed it. Yeah, there's a 12 week study. I was looking at big shell membrane daily and you did see decreased pain and decreased sickness and it led to meaningful improvements in physical function so you wouldn't be surprised because we've now seen how the individual ingredients and support joint health. So this one substance that has these three in relevant mounts had a positive effect.
Matt O. 49:13 That's awesome i'm taking this.
Dan Pardi, MS, PhD 49:15 Like everything in the body, there's usually not a single ingredient that is going to fix a complicated problem. But affecting it with a systems approach, saying what are all the various ways in which something could be supported, including all the various ways that it could that the contractions have or the breakdown occurs and can we look to support that system from multiple angles. In fact, the first product by Qualia was a brain difference, a nootropic, and that's exactly the methodology that they were considering, which is instead of like caffeine, right? If you just take caffeine, you realize that if you get a bit of a boost up to a certain point, if you take more than that, it doesn't make you perform better it makes you anxious. What if you added theanine, which is naturally sound in tease and that takes some of the edge off of the caffeine? What if you added neurotransmitter precursors, so amino acids that lend to the development of certain neurotransmitters in the brain? What if you had other natural plant substances that affect the enzymatic breakdown of neurotransmitters, keeping them present in the synapse longer? That was the whole idea of how can we support that whole system. And generally that is the methodology that is used across all their products and including this one too, which is what I like, that instead of opening 10 different bottles, you'll have fewer to engage with and that can lend itself to long term compliance.
Matt O. 50:32 Can we talk about what the other things are in this like TamaFlex®, Apflex, ginger, T3L corn, corn, HCI, Hirotaki and up in boron but.
Dan Pardi, MS, PhD 50:45 The Tamiflex is two different compounds, it's tamarind and turmeric and tamarind is this tropical tree fruit that it's that it's been used in traditional medicine for a long time and it's thought to help joint health and inflammation. Turmeric, powerful anti-inflammatory herb, lots of research backing its effects on joint health. The combo of the two shows that again, decrease in joint pain and stiffness, improved walking distance and physical function so you're seeing real world outcomes from taking it and it this can actually work faster than the undernatured collagen this can work in as level as two weeks. Again, if you take it and the next morning you wake up and you know, I feel the same. You haven't given it a long enough time for it to work. This is like a two week thing before you even begin to possibly notice an effect. The mechanisms is that as we talked about earlier with Vioxx, Vioxx shut down Cox 2 not good. This is going to down regulate Cox 2 so it's working on that pathway, but it's not doing it as powerfully and that is good because again you don't want the cardiovascular events and it also inhibits something called TNF alpha, which is a key inflammatory cytokine. So it's basically tackling the pathways of non steroidal anti-inflammatory drugs but without affecting Cox 1. So it's protecting your gut and without affecting Cox 2 as powerfully, thereby bypassing the too strong suppression of Cox 2, which leads to the cocci, the cardiovascular events over a couple periods of time. Yeah, so that's great. Then another the next one is Boswellia. This is again similar in each and herb and it's the rise from frankincense and it has pretty powerful anti-inflammatory properties.
Matt O. 52:14 That's that's the aproflex in Indian frankincense oK, sorry go ahead.
Dan Pardi, MS, PhD 52:17 Yeah, that's good. This one is faster acting where the Camouflex 14 days for that one to be working, five to seven days for Botswalia so again, you're not going to wake up the next day and look at anti-inflammatory and feel that blunted pain, but it is going to be healthier for the system. And this is inhibiting something called sidewalks and this is an enzyme that is produced by leukotrienes, produced by white blood cells. What these leukotrienes do is they promote inflammation and that then is going to attract immune molecules to the area and it's overactive. It's going to make the inflammatory situation worse, right so this is going to promote swelling if you get a little bit of an injury, you twist your ankle and it swells up. This is going to be through leukotriene synthesis. And it can definitely can contribute to chronic pain. And it's also not targeted by the pathways that non steroid or anti-inflammatory drugs target. So this is a different pathway it's complementary. It's basically a complementary mechanism of action to gomoric based strategies and then the ginger is the third anti-inflammatory compound it's again used traditionally for a long time for pain. Now we have science to back it up and this is going to shut down the inflammatory prostaglandins. Jimmy mentioned this earlier. Prostaglandins are these local hormones, if you will, that are affecting an immediate area where hormones are going to be longer acting over the entire body. This is acting more locally and this is going to affect both your CAUC system like Camouflix, but also something called nuclear factor Kappa beta, which is a major pathway for inflammation. Typically this nuclear factor Kappa beta complex is locked up in the cytosol and then when you deal with some forms of stress, it unlocks that pathway and that's going to then drive inflammation and that can be overactive and ginger shuts that down it blocks that pathway from becoming overactive. Just looking at this one ingredient in human clinical trials, decreased joint pain, decreased swelling, and it compares to a lower dose of non steroidal anti-inflammatory drugs. Sometimes we can dismiss our natural ingredients and you know, I also have better tolerance too so you're not going to get the ulcers and then gastrointestinal issues. So you can see these three ingredients are working together to reduce inflammation, pain and swelling.
Matt O. 54:25 And we talk about terataki and also the cucumber and the boron glycinate.
Dan Pardi, MS, PhD 54:32 Yeah, I don't want to overwhelm you with information, but the terataki is also an anti-inflammatory It has antioxidant effects, which can counter the breakdown of cartilage from excessive oxidative stress and it adds a little digestive support, which can help with nutrient absorption. So that's an indirect benefit. And then the cucumber extract, this is there's a standardized formulation for it called Q Actin and similarly to the other ones, only in putting ingredients that actually have evidence for them in having an impact on what we're looking at here, decreased joint pain and stiffness in humans also anti-inflammatory and then can also improve range of motion. There's been some studies that show that it actually improves range of motion. So inflammation is going to drive pain and extra swelling is going to limit range of motion. And so being an anti-inflammatory and reducing swelling, you're going to naturally get more range of motion in that joint.
Matt O. 55:24 And then what about boron glycinate and L carnitine HCI?
Dan Pardi, MS, PhD 55:30 Boron is an interesting one. There's some synergy with vitamin D. Both of those are crucial for joint health and cartilage health. It not only modulates vitamin D but also pathways and the cofactor that is supporting calcium and magnesium activity for stronger bones and joints. So this is more of a supportive role, but there are studies that show that there's decreased symptoms with arthritis when people take boron supplementation and the carnity is going to be a little bit more supportive as well this is something that affects mitochondrial energy production and everything that the body is doing requires energy. As you get older, the body makes less energy and so the body has trade-offs and it needs to make decisions. What should I give this limited energy resource to? And so our currency helps make it easier for mitochondria to make energy through food substances it's delivering it to the mitochondria so they more easily substrate to create energy. And then you can use that energy for tissue repair. Though there is actually direct evidence showing that there's a decrease in inflammation in people with osteoarthritis. That's why it's included because there is direct evidence in humans with arthritis just like boron and all the ingredients have some animal or human research that is directly looking at joint health and so that's why this formulation was put together. Does this product contain everything that we talked about today? No, you still have to take the hydrolyzed type 1 collagen, but it does do a lot of things the egg shell membrane with hyaluronic acid, the under natured collagen peptides and then a variety of anti inflammation complementary compounds with the addition of some supporting molecules. It's a really nicely designed formula.
Matt O. 57:08 That's cool. Yeah and there's curcumin in here it's just in the form of numeric.
Dan Pardi, MS, PhD 57:14 Curcumin is a phytochemical that is in turmeric.
Ginny Robard 57:18 It's the primary active compound in turmeric.
Matt O. 57:21 And it's a combination of helping you to absorb.
Ginny Robard 57:25 Yeah, yeah so the problem is that natural curcumin is very poorly absorbed when it's taken orally by itself, partly because it's not very water soluble, so it doesn't dissolve well in your gut. Thus it gets quickly metabolized and eliminated from the body. But this black pepper extract inhibits an enzyme that normally tags curcumin for rapid elimination in the gut. And by blocking this enzyme, the black pepper extract drastically slows down curcumin's breakdown and enhances its absorption like I remember one study showed that adding the black pepper extract increased curcumin bioavailability by 2000 %.
Matt O. 58:02 That's amazing.
Ginny Robard 58:03 This supplement uses a specific form of turmeric extract that is water dispersable, so it's designed to overcome the absorption issues that associated with turmeric extract by itself.
Matt O. 58:16 That's cool.
Dan Pardi, MS, PhD 58:17 Yeah, a lot of phytonutrients have incredibly powerful effects on the body, and you look at them in vitro so you put them into a Petri dish and you see the effects and they're incredible, but they can't get into the body very easily. So sensible formulations like in this case using piperine, use a black pepper extract it does actually help quite a bit. And you could be wasting your money if you don't have something that's getting into the body, even though the compound itself is efficacious once it reaches the tissue.
Ginny Robard 58:43 Another thing worth noting, curcumin is highly fat soluble, so that is another way to get around it is if you consume it with a little bit of fat like oil or like nuts or something like that that would also be a way to get around the problem of absorption.
Matt O. 58:58 Is qualia best taken at a certain point do you take it one in the morning and one at night or you take two in the morning or two at night? And do you take it with food? Could you take it with a fat like a like nuts or olive oil or something like that?
Dan Pardi, MS, PhD 59:12 Yeah i'm always very interested in the timing because I think that's it's underappreciated. We don't have that information on many different compounds.
Matt O. 59:20 Got it.
Dan Pardi, MS, PhD 59:20 But I take it in the morning and I take it with food.
Matt O. 59:23 Got it.
Dan Pardi, MS, PhD 59:24 Yeah.
Ginny Robard 59:25 Yeah, because this particular version of curcumin is water dispersible. It's designed to enhance absorption without needing to rely on either black, the black pepper extract or fat.
Matt O. 59:36 Cool.
Dan Pardi, MS, PhD 59:37 So we covered a timing. I have other stuff that we can discuss. Icing an injury, icing a joint aside from taking non steroidal anti-inflammatory drugs or getting a cortisone shot, icing an injury is something that we do a lot. Stenolytics products that breakdown senescent cells, peptides so things like BPC one fifty seven thymosin beta four or TB five. Hundred that's his nickname thymosin alpha one aod nine six O four, even one that's not really a peptide, but you can include it in the discussion is something called pentosin polysulfate Sodium stalina. Red light H VOT hydrobaric oxygen radiation like from a radio oncologist. Now low dose radiation therapy or LDRT is being used on joints so you might do let's say 6 different sessions, three one week and three the next. And this is having pain relief on tendinopathies, on osteoarthritis that lasts for months to years.
Matt O. 1:00:35 I'd, I'd love to have more conversations. We've talked about SAW and I'd love to talk more about peptides and red light and also stem cells and PRF.
Dan Pardi, MS, PhD 1:00:44 Why don't we make time again in the next week or two, we'll cover some of these other topics because they're interesting. And what we're also going to do is create a how to died for you that has less on the education as to the why, but condenses it down into the how. Like remind me of the dosage, remind me of the time under exposure. And we're putting that together that should be ready soon.
Matt O. 1:01:04 Thank you.
Ginny Robard 1:01:05 Maybe we should quickly recap what our recommendations are i feel like we covered a lot of stuff, but actually the joint health maintenance plan that has emerged from all of these notes is actually not that complicated. Go ahead. I think so. So with the collagen peptides, we're suggesting A2 pronged approach where your day you're taking at least five grams daily to support connective tissue maintenance and then after resistance training you're taking a mega dose of 30 grams to help promote tendon adaptations and then.
Dan Pardi, MS, PhD 1:01:37 You're OK with before or after, but hairy exercise?
Ginny Robard 1:01:40 Hairy exercise, yeah, I guess that's the correct term for it. And then obviously the quality of joint health, it just really covers all three pillars of joint resilience that we talked about. It provides structural support through the egg shell membrane, which contains under nature type 2 collagen, promoting immune tolerance to joint cartilage as well as the elastin which supports tissue flexibility, resilience. Then the hyaluronic acid in the eggshell membrane promotes both lubrication and nutrient delivery because it improves that synovial fluid viscosity, promoting exchange of nutrients and base, which is important for cartilage health because cartilage is a vascular And then inflammation balance through all of the different compounds that Dan explained, like the Tamiflex, the tamarind plus the turmeric, the Boswellia through the Opreflex and the ginger. And then all of those additional ingredients that we talked about like boron, elk, carnitine, haritaki, and the cucumber extract all contribute a little bit on all three of those pillars. So yeah, it's actually not that much like.
Matt O. 1:02:46 Collagen 5 grams a day.
Ginny Robard 1:02:47 Yeah, it's actually not that much.
Matt O. 1:02:49 Keep moving.
Dan Pardi, MS, PhD 1:02:51 Yes, Matt, great summary perfect what I said in the very beginning is that there's a couple of challenges here. The ideal time to start this is before you feel the issues, but it's also great to start it when joint health becomes more important to you, which is usually when you start to feel some of the effects of joint breakout. Yeah, for those who are bought in, starting to take this in their thirties even earlier is great. And then being patient so if you do have some joint.
Matt O. 1:03:18 Health What would it take as a teenager?
Dan Pardi, MS, PhD 1:03:20 Yeah i mean, it's providing structural support and then you do want to be careful around anti oxidant, anti-inflammatory But what I like about natural compounds taken in reasonable doses is that Judy said it nicely, they're supporting inflammatory balance and that's what we want. We want to be able to keep your inflammatory processes healthy so that they can clear debris and work functionally, but you're also then preventing chronic inflammation and that is going to be a good strategy throughout life.
Matt O. 1:03:48 Yeah, cool. Thank you, guys. Really appreciate you guys taking the time.
Dan Pardi, MS, PhD 1:03:53 We'll chat with you, Matt, I'll follow up. We'll let you know when that how to guide for joint health is done so that you have that as a reference.
Matt O. 1:03:59 Perfect that sounds great.
Dan Pardi, MS, PhD 1:04:01 Have a great weekend.
Matt O. 1:04:02 Ok, have a great weekend bye.