Dr. McEwen: So, first off, I’d like to start by saying I’m very excited about doing this podcast. And I believe that, you know, everyone should have some. Everyone should have some vitamin K2. And, to finish off with that, thank you very much for all your attention. Sorry, just a side joke.

So, this is, the exciting thing about vitamin K2, as what you’re saying, Andrew, is it’s a very wide field of information. And if you think of it in a way as yes, there’s vitamin K1, vitamin K2, but why should everyone be having some, and what is so special about it? And one of the areas I want you to think about is let’s start back at the beginning, looking at structure, function, biochemistry. Put that in your mind as we go through today’s journey. I’m gonna say today’s a journey through vitamin K2, because we’re gonna cover a wide range of different areas.

So, as we go through, think of structure, function, biochemistry, and what’s linking all these things together. Because if you understand that, you’ll have a better understanding of, you know, health, and nutrition, and sort of naturopathic medicine in general. So, when we start thinking about, you know, vitamin K, vitamin K2, etc., what is it? So, the two main ones we look at is vitamin K1 and vitamin K2, named normally, in numerical order, as like the B vitamins, that sort of goes in order of when they’re found. So, one thing I want you to think about is vitamin K1 has a phytol side chain. So, it’s sort of like a lipophilic side structure, and that’s its main differentiating point. While vitamin K2 has more, like, a carbon chain, carbon bonding type of effect, where we’re looking at sort of these repeat molecules. And that’s the main difference structurally between the two. I know it sounds sort of simple. One’s more of a lipophilic, and one is more of a sort of carbon-based structure, but that actually helps benefit the differentiated two of how they work.

And we always see things like, you know, what is the difference between menaquinone-4, menaquinone-7, menaquinone-10? There’s all the way from, sort of, number 2 to number 14. And that’s all based on the number of side chains. So, there’s your biochemistry, very easily. It’s just a simple thing, as in how many side chains does this have? And in this case, MenaQ7, which is the focus of what we’re talking about today, has seven. So, I want you to think, sort of, you know, how do we get this? Where does it come from? So, vitamin K2, particularly menaquinone-7, is formed in the gut. It’s formed in our bacteria, so we can actually manufacture part of it ourself. And in fermented foods, of course, from the bacteria of the fermented foods. So, that sort of takes us back to, you know, it-all-happens-in-the-gut effect, you know, how we talk a lot about naturopathic medicine, is, a lot of symptoms, and systems, I should say, work from the gut out, inside out.

So, if we keep that in mind, that’s a very big area. If we have good digestive health, we’ll have better digestive health related to our vitamin K2 metabolism, particularly MenaQ7. So, I want you to start thinking about comparing the pair, if you think about this. So MenaQ7 is, we’re looking at absorbed in the large intestine, while vitamin K1, phylloquinone, is actually absorbed into the small intestine. So, that’s sort of, like, the small differences, to start with. And as we go through the different processes, vitamin K1 and vitamin K2 are both sort of absorbed and utilized into our chylomicrons, into our LDL cholesterol as well. So, we always tend to think of LDL cholesterol as being, you know, the bad guy, causes all these problems. But I try and think, “Hang on. LDL actually does play a role in the body.” It’s very useful for, you know, fat-soluble vitamin-carrying, such as K2, but also other nutrients as well throughout the body. So, it actually has a wider role.

So, if you think about this, vitamin K2, and K1, gets absorbed in our gut, gets attached, and enveloped, I suppose, by the chylomicrons, and deposited throughout the body. And particularly with K1, it goes into the body, gets picked up by the VLDLs, and gets taken back to the liver, where it tends to, let’s say, live its life. Vitamin K1 particularly does a lot of functions in the liver. The difference with vitamin K2 is it tends to utilize the LDLs a lot more easily, and transport to what we call the extra-hepatic tissue, so, outside the liver. So, vitamin K1 stays inside the liver, essentially, after absorption, and vitamin K2 goes throughout the body. And that’s what makes it different as part of our clinical side that we’ll talk about later.

The other thing that’s exciting about vitamin K2 is it crosses the blood-brain barrier. So, that’s something we can start thinking about later on when I talk about plaque-forming and crystal-forming conditions. Think of Alzheimer’s, or multiple sclerosis, etc., that it could actually have greater benefit in. So, everyone always thinks with K2 is blood and bones, which is good, good to think that way. But what we’ll be talking about in this podcast is, you know, good bit more than that.

Andrew: Yeah. Okay. So, a couple of questions straight off the bat. If we’re talking about in MK-7 being incorporated into the LDL molecule, does it have any protective effects there, like, for instance, ubiquinol does, protecting the LDL against, the LDL particle, against oxidation and therefore foam cell production? Do we have any evidence that MK-7 has that sort of protection against atherogenic molecules?

Dr. McEwen: It’s an area I haven’t looked into yet, but it’s quite exciting, because I like the ability of how vitamin K2 does have that antioxidant effect and cell protective effect. And if you were to combine it with ubiquinol, tocotrienols, for example, and other similar antioxidant molecules, you could predict, from small, dense LDL, like, the golf-ball effect of it smashing into the arterial walls. So, from my thinking of, going back to, like I mentioned earlier, our structure, function, biochemistry, short answer is yes. I think, from what we understand, it will do that. It’s not an area I’ve looked into, but I will now. But it’s something that I think will actually make a big difference of our understanding of how vitamin K2 does that work.

Andrew: Yeah. And, another one. Sorry, Brad, to go straight off the back, because you piqued my interest, and that was, when we’re talking about being incorporated, or helping the liver, do we have any evidence yet that vitamin K2 MK-7 might be beneficial in conditions, metabolic conditions, like, well, we used to call it non-alcoholic fatty liver disease, but we realized that there was too many people drinking, not having non. So, I think the acronym is now “MASLD?” Is that right? M…

Dr. McEwen: Something like that. Yeah. There’s a lot of extra letters.

Andrew: Metabolic-associated…metabolic-associated… Don’t know what the S in there, liver disease. MASLD. Yeah, I think the acronym’s changed, but do we have any evidence yet that MK-7 is a benefit in those conditions?

Dr. McEwen: Not that I’ve seen, particularly, like, related to what you’re saying, but if you look at the wider aspect of how non-alcoholic fatty liver disease, or fatty liver disease, cirrhosis, or any of these liver diseases work, the short answer, again, is yes. I believe it will actually have great benefit in that area, because it is working through, you know, the regulation of cholesterol metabolism, antioxidant/anti-inflammatory pathways, calcification pathways, which I’m about to talk about. So, I do think that, you know, we are gonna see more benefit in that research. The main sort of focus of research of K2 that we’ll be covering has been extra-hepatic. They haven’t really been looking at the liver. But if you think of the vascular system, of course, the liver is very highly contained of vascular tissue, so that’s how, part of the filtration unit effects. So, with my understanding of how it works, it would definitely greatly benefit. And there is research with tocotrienols, for example, of reducing the impact of non-alcoholic fatty liver disease, or fatty liver disease, adiposity-based conditions, which is where…there’s a new condition base, ABCD they call it, which is, sort of, adipose, B, because I can’t remember, because I just thought of it, cardiovascular disease. Like, they’ve tried to do, like, an alphabet kind of thing, where each letter means something.

Andrew: Yeah, yeah.

Dr. McEwen: And it may have been adipose-based. It may be as simple as that.

Andrew: Yeah, right.

Dr. McEwen: But it’s where you start thinking about, you know, when we do have adipose tissue, whether it’s in the gut, or the liver, or around the heart or brain, or any other area. You know, it’s on fire, and it’s causing some inflammatory effects. And if you think of any way that can greatly benefit the blood flow, the antioxidant/anti-inflammatory capacity, which vitamin K2’s working in the background of, I think it would greatly benefit in those situations.

Andrew: Yeah. Okay. So, K2. Then we’ve got the different molecule lengths. We don’t have it here, as is my understanding in Australia, the MK-4. The one that we have available is MK-7. But the molecule lengths go right up to, what, 13 or something? Is that right?

Dr. McEwen: So, 13, and recently 14. So, we’re finding, you know, a lot more research as we go through, and that’s the benefit of, you know, where we’re going with nutritional medicine and naturopathic medicine in general. So, it’s not just science, you know, research of course, but it’s how we apply it. And that’s where, in the year that we’re in, it’s very exciting to see a lot more research come through. And there is some MK-4 research out there. So, menaquinone-4, they tend to call it “MK,” so, menaquinone, K2, and then they break it down into its numbers. MK-7 is menaquinone-7, MenaQ7. So, if you think about it, the lower the number, the shorter the molecule. The longer the number, you know, the long-chain kind of effect. So, if you keep that in mind, that seems to be the way how it works in the body, where the longer numbers seem to be more flexible. So, particularly, MK-7, menaquinone-7 being in that mid range, it is classified as a long-chain vitamin K, so I want you to start thinking about long-chain fatty acids, etc. It’s the same kind of thing with K2, is you’ve got different lengths doing different things.

And a lot of the research is still based on this, sort of, menaquinone-7 effect, because they’re find that’s where it has the greater effect, because it seems to have that, sort of, more bio-flexibility of the molecule, compared to the longer chain and the shorter chain, and being in the middle, it seems to have that greater effect, even though, as I said, it’s still classified as a long chain. And what I’m thinking about is, as we go through this podcast and general conversations, is there’s always new ideas coming up, like, the more we think about, with, you know, biochemistry. And it’s a very good question, you know, with the length of the structure, and how it works in the body. Again, thinking of tocotrienols, with the biphytol tail, it’s able to move its way into the fatty tissue, into the cell membrane, work antioxidant inside and outside, anti-inflammatory, inside, outside, outside-in. So, it sort of goes both ways. We’re finding that a lot more with vitamin K2 now, is it’s, I’ll use the word biphasic, where it’s able to cell-signal inside-out and outside-in, to incorporate a lot of these changes. It’s quite exciting.

Andrew: Right. Yeah, absolutely. If you’re thinking about food sources, though, I, like, I have not looked into this at all with regards to chain length. All I’m aware of is things like natto, hence natto pharma. But, from the natto beans, with, what is a, Bacillus subtilis fermentation. And then there’s cheeses, as well. Swiss cheeses. I don’t know of any other source, and I don’t know about if, either, or which foods are more linked with different side chains. Do we have any knowledge of that? Like, you said, like, we’ve now elucidated a side chain of 14, so an MK-14. Do we know what foods that’s from? Or is that only from, like, fermentation of bacteria in the gut?

Dr. McEwen: Seems to me more from fermentation in the gut, but also they’re finding it in some fermented foods. So, going back to the natto, which is a fermented food, I’m thinking, yeah, let’s jump ahead or back, in this case. Things such as, you know, sauerkraut, and other, just, general fermented foods that have been around a long period of time, we’ve always used them for digestive health for centuries, and not really knew how they worked. And we’re still finding out more and more details about fermented foods. So, it makes me think, you know, vitamin K1 is mainly found in green leafies, for example. That’s one of the main sources of it, as we’ll, working on earlier, and K2 is more in fermented foods, so I’m gonna suggest any major fermented food, with that sort of, you know, Bacillus that we’re just talking about, that seems to be where it’s found. And, again, in our gut. So, we’ve got a whole ecology working with us, or against us, in some cases, that could be working with metabolizing.

Andrew: Yeah. Okay. So, the uses. If we go into, you know, the, I think the initial work was done on bones, but then it took a side thing, and was looking at cardiovascular disease. There was other potential uses as well, depending on the, what is it, the proteins they’re working on, is that right?

Dr. McEwen: That’s right. So, there’s a number of different areas. So, what I was thinking of, because when we were originally talking about this, I was thinking how can we go about, you know, discussing the benefits of vitamin K2 in a short amount of time? Because we could talk all week about this. And I was thinking, yeah, let’s go through some base health conditions first, and then sort of, you know, expand on those. So, the main functions, or uses, of course, is improving bone health. That’s one of the main areas that they looked at. You know, reducing fracture risk, there’s a lot of research on that, vitamin K2, because everyone always thinks, you know, calcium and the vitamin D. That’s great, because that does have a lot of evidence, even phosphorus, or phosphates, for the bone structure matrix. But you also need something to sort of direct and work things out. As in, I see vitamin K2 as a director in a lot of these areas. So, whether it’s blood, bone, other tissue we’re about to talk about. And that’s what I like, and find exciting about vitamin K2, is that it is like the director.

So, we’ve got other areas, such as blood coagulation, which is well-known. We keep looking back into that. Just overall cardiovascular health, reducing cardiovascular risk and mortality, reducing vascular calcification, which we’re gonna be talking about shortly, reducing arterial, sort of, stiffness. So, I want you to imagine the cardiovascular system is like a hollow tube, as we know. And if the hollow tube is flexible and flowing properly, we have good blood flow. Once it becomes sort of stiff, and sort of more restricted, that’s when you get your hypertensions and your hemorrhages, and your vascular depletion, strokes, heart attacks, DVT, etc. Metabolic syndrome. There’s a lot more research there, where vitamin K2’s working hand-in-hand with insulin, which is pretty cool. So, remember, we’re moving away from the original side now. Improving chronic kidney disease, which could also be related to, you know, type 2 diabetes, vascular, you know, wide range of different health conditions, of course, with chronic kidney disease. Kidneys are very tough. You don’t normally notice there’s a problem until there’s a big, big problem.

Andrew: Pain, yeah.

Dr. McEwen: And, yeah, they don’t feel pain too much, so therefore they either have to be really large or really small, and, sort of, I’ll use the word damaged, for them to actually tell you that there’s a problem with themselves. They’re quite tough. And also, just reducing age-related chronic disease states, we’re finding out. So, you know, in the last decade or so, there’s been a very big push for vitamin D3, and, you know, vitamin D3 markers, and having X amount of, in the blood, for example, when you do a blood test, should we be also measuring for vitamin K2, because they work in a similar pattern of chronic disease prevention or risk reduction? So, I was thinking, sort of, taking us on a bit of a journey through vitamin K2, if you like, about how it works. I like stories when it comes to this, because it helps me you remember how it works.

So, I want you to start thinking about, you know, vitamin K2 is a multifunctional molecule. Multifunctional nutrient, vitamin. So, yes, it starts with the bones. That’s where we know. But actually starts working at a lot of wide range areas as well. So, it works with a lot of enzyme pathways. So, one of them’s, and I’ve written down some notes, so I remember how to say them right. Gamma glutamyl carboxylase enzyme pathway, which sort of works with glutamic acid. So, carboxylases glutamic acid. So, CO2H bonds, etc. It seems to work, you know, with functionality there. It works with, I love this name, vitamin K-dependent proteins. I’m like, whoever thought of that name one day was on fire. It’s like naming Sydney Harbor, Sydney Harbor Bridge, and Sydney Opera House and Sydney Cove. Like, yeah, those people get paid big money.

Andrew: Great sandy desert.

Dr. McEwen: Great Sandy Desert. Let’s [inaudible 00:19:28]. Western Australia, Northern Territory, South Australia. They did really well. So, this day, this person was on fire, and called them vitamin K-dependent proteins. So, that really works for me. So, it says what it is. So, one of these particular proteins that works with the, I’m gonna call it the glutamization, new word of the day. Doesn’t exist. Glutamization is osteocalcin. So, we do know osteocalcin. So, if you, whenever you’re trying to understand a word that you’ve never heard of, and this is for a lot of our viewers who may be starting off in their careers, break it down. Osteocalcin. Osteo, normally meaning bone, calcin, calcium. So, transportation of calcium. And it’s synthesized by the osteoblasts. The osteoblasts, of course, are bone cells that form and create things. So, this is forming during mineralization phase of the bone. So, osteocalcin’s very important for bone health. And it binds to the calcium ions, and the hydroxyapatite crystals regulating size and shape.

So, I want you to imagine, because we’re gonna stick with the bones. Let’s start with the bone matrix. One of the main stages of working on bone matrix is between the ages of 8 and 10. So, Andrew, you and I are a little bit gone past that point of ages 8 and 10, but we can still keep working on the regulation of that, because up until about the age of 21 to 25, which is the category that you and I are in, it seems to be still forming, and working to get that sort of solid effect, you know, solidifization for the rest of our life. But what I want you to remember is we’re always building, breaking down. That’s, nothing is ever set in stone, so to say, because red blood cells, 120 days. Like, platelets, 7 to 14 days. Like, things are always growing and developing. We’re growing and developing from the moment we’re conceived, the conception of who we are, all the way to the end. We’re always growing and developing in all different areas. Everyone always thinks mentally and physically, for example, and emotionally growing, but physically, the body and the biochemistry’s always growing and developing. So, our bone is always in this constant state of flux, where it’s always moving, and it’s regulating, and it’s changing.

So, if you sit down and do nothing all day, your bone mineral density will change, probably go to your buttocks, because you’re sitting on it all day doing nothing. But if you get up and become active, and that’s the comment I made about ages of 8 to 10, up to 11, because you’re physically active and you’re actually impacting and pounding on that bone, and gymnastics and tennis, and a lot of these force activities create that bone strength. Swimming doesn’t, of course, because it’s not weight-bearing, those kind of activities, but anything that’s moving, including just walking, starts that process. So, getting up and moving. And that’s when we start to develop, and those crystals then start to form, and our bone starts to form shape to where it needs to be. So, whether it’s a long bone or a finger bone or anything else like that. Again, it’s the old, “if you don’t use it, you lose it” kind of mantra that we say with a lot of things.

So, if we keep working with this osteocalcin, and this is where we start to visualize in our mind, that it’s sort of creating a higher affinity to this hydroxyapatite, mineral bone content, and it’s actually driving in calcium, and other nutrients, of course, into the bone tissue. And that’s what we really want. So, I want you to start thinking this is like a link between geochemistry and biochemistry now. So, I want you to start thinking because, you know, geochemistry is all crystal formation, minerals, etc. So, in some cases, some people are just big, walking crystals, you know. I want you to think about that. So, they got the bone mineral density that’s changing. They may have gout, which is crystals as well. So, there’s a lot of areas that sort of start thinking about crystal formation, and it’s going to the wrong place. And osteocalcin, being driven by vitamin K2, and of course, vitamin D3, is working on this journey.

So, again, we’re sort of working with visualization of bone-forming, and other tissue utilizing it. And if we think of that process, we can start thinking about what else happens. So, osteocalcin then starts working with energy metabolism, bone metabolism, endocrine function. So, all the different endocrine organs are starting to become involved. So, this is all part of our metabolic health. Because our bones are metabolic, our blood is metabolic. So, if you think about, you know, regulating energy metabolism, and just overall health that way, it starts working.

And another role, which we’ll talk about later, is it has this inhibitory role on angiogenesis. So, angiogenesis, of course, is the formation of new blood vessels, and we want that to happen, you know, for general health, but we don’t want that to happen in cancer, because the generation of new blood vessels means blood flow for the cancer cells, which means growth and development of them, leading to cancer formation, as a brief storyline. It also regulates ectopic tissue calcification. So, ectopic always means away from, sort of, where it should be. So, in this case, we’re talking about blood vessels. So, there’s, you know, a wide range of different areas that we’re working of, just with the osteocalcin side, and it’s a transporter. And we’re journeying through the body. And that’s what I like start to think about, all these vitamins and minerals and amino acids and everything going on a journey, for our nutritional needs. Yeah, there’s another protein, there’s the matrix GLA protein, that keeps working with this, and that works with the cardiovascular disease health.

Andrew: So, the matrix GLA proteins, Brad, can you tell us more about those? What they do?

Dr. McEwen: So, again, I want you to think about, you know, the terminology “matrix GLA.” So, we always talk about the matrix, not the movie, but the actual matrix in the body, where it actually works by, it’s like a netting, a structure. It’s hard to explain sometimes without using too many hand motions. Cellular matrix, tissue matrix, organ matrix. It seems to work by, you know, piecing and putting things together into its cell structure, into its, yeah, system. And that’s what I find interesting, where there’s this communication between cells that are the same cell, but also other cells. The body has this amazing communication with itself. It’s just, and again, in today’s year, it’s, we’re still finding out the way how, you know, I’m fascinated by how things work, how we can talk and think and walk and text, and do all things all at the same time, and it’s the body’s, you know, matrix system itself working and communicating with each other, and this GLA matrix is one of those areas. And what I was thinking about, as I mentioned earlier, it’s sort of going through a bit of a journey into, you know, applications of how we could utilize, you know, menaquinone-7 K2, and you gotta say it slow.

Andrew: So, the evidence. We started off with earlier work by Theuwissen and his group. His group? What is the evidence now showing us? Because there was some positive, some negative evidence. But when I looked further, it was kind of like, what was one of them? There was a positive change in the lumbar vertebrae, but a negative change in the…was it radius, radial? Density? Radial bone density? So, it’s sort of like, it’s almost like what you were talking about earlier, about that need for exercise. Now, I don’t know about this. It was just an interesting thing. Tell us more about the research, and where it’s leading us.

Dr. McEwen: And that’s the exciting thing. There’s a lot of interesting things that we can really, you know, move into as we go through. And I want you to think back. Most people now are becoming more sedentary, over the last few decades. We’re working more inside, less active. I have my Apple Watch, where I deliberately have it set where I have to get up regularly, and move around, so that’s keeps the circulation going, keep the body going metabolic-wise. And that’s what I’m thinking back to that study that you’re mentioning, that the lumbar region is being used more, because you’re sitting on it, for example, and you’re using it more as weight-bearing, while your wrists may be on the desk, they’re not really working as much. You may be typing or using the mouse, but it’s not weight-bearing, as compared to your lumbar.

But if you start exercising more, and actually moving, moving and grooving, and moving around, you start to use that. And that’s where some people use weights, you know, like the wrist weights, or just do that. That’s weight-bearing still. So, holding and using a mouse is not weight-bearing, but it’s sort of, like, any kind of activity. So, you know, if you need to get up from your desk and do, like, the old 1980s sort of aerobic exercise around the office, where you’re punching the air and moving around, because that sort of gets things up and moving, and then you can add some weight-bearing to that.

So, what I’m thinking, if I go through some of the research that this is leading to…

Andrew: Please.

Dr. McEwen: …and then we can have a good discussion at the end, because it’s sort of quite exciting where we’re going, and part of that is, of course, you know, cardiovascular disease. We’re looking a lot more vitamin K2, menaquinone-7, with cardiovascular disease. So, one of the areas I mentioned earlier is, you know, coronary artery calcification. So, what is it? The name it says, and we’re very well-named. Coronary artery is calcified. There’s a calcification process happening, and it’s a very significant predictor of cardiovascular disease and cardiovascular disease risk. And there’s some pioneering work in that area, where you can look at calcium scores, etc. So, one of the areas we’ve been looking at is a deficiency of vitamin K2 has been linked to vascular calcification. Not just coronary, but just overall vascular calcification.

And if you think of it this way, you’ve got different mineral deposition, particularly calcium, of course, coming from the calcium hydroxyapatite, and we always say from the bones, because that’s the main storage site, into the vascular system, and then going into the vascular wall, because it gets trapped. So, it’s like a big centrifugal force, going through the arteries, and then it just gets trapped because it’s, I don’t know, heavier? It’s like a big metal going through, and it embeds in there over time, as you know. We’ll talk about foam cells, atherosclerosis, etc., and it starts that calcium, you know, process. And this deposition also combines phosphates, other minerals. I’m gonna suggest even heavy metals get involved. I had a patient many, many years ago that had an issue where no one could work out what it was. And we ended up working out, long story short, the GP came in with her, and it was a very serious case. And her files were, can’t see my hands, but really massively printed out, every test under the sun. And I just talked about, you know, bone deposition, everything that was sort of mentioned today. And what I found out was, due to the childhood, there was different heavy metals in the area. And that’s what deposited into the tissue. And when she moved around that tissue left, because she didn’t have enough vitamin D, vitamin K, etc., and then left the bone, so she had bone pain, and then embedded into her vascular system, leading to cardiovascular risk.

Andrew: Right.

Dr. McEwen: So, that was a good example of someone that had heavy metals as well. And metals combined with metals, if we go back to our anions and cations and everything else like that, they all, the biochemistry all combines together, leading to this complex, which then sat in the arteries, and it can sit in the basement membrane of the artery, or it can be on the inner or outer side of that membrane, leading to an inflammatory process, an oxidative process, leading to, like, a firestorm in there. The body tries to heal it, by laying down, you know, fibrin, and different connective tissue, to help protect it, putting a Band-Aid down, I suppose. And then that’s when you get your atherosclerosis, your plaque formation, and then, you know, your eventual clot in that area.

Andrew: Yeah. Yeah.

Dr. McEwen: So, it’s a big process. So, if we think about that as occurring, and then we reverse that process, by thinking, okay, we’ve covered today thinking about vitamin K2, and how vitamin K2 works with osteocalcin, crystal deposition, you know the microcrystalline fibers in the body, and then you got your cell matrix, and hydroxyapatite, we can then start moving and directing. As I said, Vitamin K2, to me, is a director, directing it to the right place. And it sounds very, sort of, story-like, but it’s, that’s the way how a lot of our body works. It’s a big story that’s being directed by our DNA. The main director, like our genetic code, is telling everything what to do. So, if you think about, you know, that different process, just with this, calcium, you know, fortification in the coronary artery and other areas, we can start thinking about vitamin K2, and how that can benefit.

And there’s a lot of different research studies coming out of, you know, the really long, long longitudinal studies. So, these studies have being going on, you know, like the Framingham Heart Study, the Lyon study, the Nurses’ study, the Health Practitioners’ Study [crosstalk 00:33:19] Nurses. There’s a lot of research studies now where they can look back over test results from the past. There’s blood samples from the 1940s and 50s and stuff that they can actually pull out of -80 freezers, and actually test it for new inflammatory mediators that were never around even 10 years ago. So, they’re able to do a lot more of this research. And a lot of research is starting to show, not with just those kind of studies, but other studies, that vitamin K2 depletion, over a period of time, has led to higher risk of, you know, arterial calcification, as well as just general calcification of the body in the wrong areas.

Andrew: Yeah, yeah. This is one of the areas that interest me, in that, when looking at the research, some of this negative research was coming out, saying that vitamin K2 MK-7 did not reduce coronary artery calcium score, but I know, clinically, it damn well does. I had an elderly gentleman who had a, I mean, you’ll fall off your chair when you hear this coronary artery calcium score, a CAC. It was, the CAC was originally something like 5000. Now, I haven’t got the things directly in front of me, but it was something in that vicinity, whereas anything over 400 is of clinical, like, huge clinical significance, 15% risk.

Dr. McEwen: Clinical significance.

Andrew: So, this was in the thousands. Upon taking…now, I’d have to work out the exact dosage. Forgive me, but on taking around about 5, 6…so, let’s say 300… Forgive me. Six hundred micrograms of K2, combined with 6000 of vitamin D, plus, there were some other supplements in there because of the health conditions of this gentleman. Within a six-month period, his coronary artery calcium score was reduced by half. Now, that’s still massive.

Dr. McEwen: It’s still massive.

Andrew: It’s still, you know, 2500. But that is a significant reduction in risk. And there was a further…

Dr. McEwen: So, this person was leaching [crosstalk 00:35:37] bone.

Andrew: …reduction… There was a ticking time bomb. And, you’re right. You’re right. Leaching bone. So, it makes me query the “evidence,” where they say “no, it didn’t,” when I’ve seen it work like that. It definitely does reduce CAC.

Dr. McEwen: It definitely does, and, dose, we’ll talk about later, because I’ve got a couple of points I wanna make on dose, you know, very specifically, for what, you’ve led into it very well, actually, where I’ll talk about a couple of clinical cases as well. So, what I’ll do, I’ll finish off this journey, and then I’ll talk about the reasons why I believe that those doses do work in some cases and don’t work in others, because it’s sort of, once we have an understanding of, you know, where this journey’s going, you’ll see why certain doses work. And that goes for with any nutrient, any herb, of course.

So, if we continue through our turbulent journey of our vascular system, forging ahead, you’ve got arterial stiffness as well. So, you got your calcification, you got the stiffness. Now, thinking about that person you just mentioned, they’re turning to stone, with that calcium score. It’s a very high calcium score. So, they’re literally turning to stone. So, arterial stiffness, as well as, you know, vascular calcification are very good predictors of cardiovascular, and overall health, I’m gonna say. So, a lot of test results can let us know overall health. So, there was a Knapen study, which is quite well-known. It was a double-blind placebo-controlled, and I’ve gotta get the number right, and I’ve got it in front, 244 healthy postmenopausal women, because you always gotta throw in the healthy part. So, healthy typically means that they don’t have the condition that they are testing for. So, in this case, it was 244 healthy postmenopausal women. They investigated the effect of vitamin K2 at 180 micrograms a day, which is a standard dose that we use in Australia. A hundred and twenty in that, and placebo is 124 people, for three years.

So, having any nutritional study for a month is pretty good. Six months is really good. Three years is really, really good. So, the longer the research studies, the better. So, after three years, they found that K2 improved arterial stiffness, so, the artery’s more flexible. So, sometimes we have to be careful when we say improved, because the word can go both ways. So, improved arterial stiffness, especially in those with already high arterial stiffness. So, it sounds quite interesting that, in the people that already had a high level of arterial stiffness, they had a good, a very good improvement in their blood flow, and a reduction in their arterial stiffness, at that dosage of 180, versus what you’re mentioning earlier. They seemed to have also had a reduction in, yeah, the GLA protein matrix area that was seen to be having a negative impact. So, the flow of calcium in the body would seem to be more improved. So, that’s just one study. There are quite a many more we could talk about, but due to time, I’m trying to, you know, have greater examples of each one.

If we go from arterial stiffness to a wider range of condition now, called peripheral artery disease, or arterial disease. So, we’ve gone from calcification, to arterial stiffness. Now we’re looking into a disease state name, I suppose, and this is our journey. So, peripheral arterial disease, or artery disease, is actually more common than you think. So, think of the name. Peripheral, so, legs, arms, hands, feet. You know, arterial, just arterial blood flow, and disease is just dis-ease. It’s just a condition base. Now, what they’ve realized and worked out with research, again, with longitudinal studies, that a low vitamin K2 status has been associated with increased risk of peripheral arterial disease. So, again, they’ve been looking at a lot of studies. So, here’s a little study for you, Andrew. Sorry about that. A 12-year study. So, here we go, 12 years, on vitamin K2. So, this was the intake, measuring the intake, on a small number of people, 36,629. So, here we go. This is where we want the guts of things now. So, this is where we really see some really good research come through.

At the end of 12 years, vitamin K2 intake was associated with a reduced risk of peripheral arterial disease, with a hazard ratio of 0.71. So, what this means, for the audience, is hazard ratios are quite interesting to look at. If you think about it, if you have a hazard ratio of 1, you’re likely to get it. If you have a hazard ratio of 1.5, you are 50% more likely to get it. In this case, we are 0.71, meaning there’s a 29%, because you take that from 1, 29% less chance of this happening. So, that’s the hazard ratio. So, I think that’s a pretty good number, that, you know, your vitamin K2 status over that period of time meant you had a 29% less, you know, chance of this happening. Ten percent, for me, is great, if you know what I mean. Statistically, of course, the higher, or in this case, the lower the hazard ratio, the better. High blood pressure was measured in this study as well, because they measured a lot of different areas. Hazard ratio is 59, sorry, 0.59. So there was a 41% reduction in risk. Type 2 diabetes had a hazard ratio of 0.56. So, again, we’re looking at a 44% reduction. So, this is just from the humble intake being measured of vitamin K2. So, I think it’s quite exciting to see, you know, a lot of this base research being done. Of course, it’s large numbers when we get this. But something very interesting for me, going back to where we first started, the intake of vitamin K1 had no association with reduction of peripheral arterial disease.

Andrew: Right.

Dr. McEwen: And why is that? Think back to when we first started.

Andrew: It’s different molecule length, but… Yeah. But, I mean…

Dr. McEwen: Different molecular length?

Andrew: But not just molecular length.

Dr. McEwen: There’s an answer.

Andrew: Like, it brings into question things like methylation as well…

Dr. McEwen: That’s it.

Andrew: …on treating an existing condition.

Dr. McEwen: So, there’s…the winner of this gets a copy of my book to be published. This is a question for the audience. You get a prize, but I’ll give you the answer as well. So, at the beginning, vitamin K1, I mentioned, is intrahepatic. It mainly stays inside the liver. Vitamin K2 is extrahepatic, meaning it goes out to the tissue. So, vitamin K1, for example, in these patients, stayed within the biliary, stayed within the liver system. So therefore it would generally not have an impact on peripheral arterial disease because it’s in the periphery. While vitamin K2, floats, we’ll use the word floats…floats around the body on our LDLs and chylomicrons and everything else like that, so therefore it’s able to achieve its point. So, there’s a good example of where K2, being extrahepatic, is able to do something at the far ends of the Earth, being the hands, feet, legs, and arms. So, goes back to, like I mentioned earlier, structure, function, biochemistry. Every time we need an answer, think back. The answer may not be scientifically proven yet, but we start to think back in, what are we thinking about? It’s the physiology, the background work. In this case, that’s my answer, is K2 did the job, because it’s extrahepatic. It went outside the liver, and did its job, rather than inside the liver. They didn’t do any hepatic markers, which would have been interesting to see, of course. But, you know, that’s another study to be done. I could, well, Andrew, both of us could sit down and write a whole heap of studies about what we’d like to research right now. It’s quite exciting.

Andrew: Brad, we spoke earlier about doses. We need to cover this off. What doses are appropriate? Can I quickly ask, by the way, that large study that you were talking about before, was that the Rotterdam study, or was that a different one?

Dr. McEwen: It was a different one, and I can’t remember the name right now. But it was a different one. [crosstalk 00:44:34]

Andrew: No, that’s right. They all have different acronyms. That’s fine.

Dr. McEwen: They do.

Andrew: Can we cover off on dosages? Because one of the things that’s interesting me is, out of convenience, we tend to combine D3 and K2, but the more I learn about K2, the more I’m wondering about the formulae on the market. Are we wasting the K2? You know, are we taking, not too much, necessarily, but are we just wasting the dose? Should we indeed be taking D3 separate from K2?

Dr. McEwen: That’s a very good clinical point. When I was think…sorry, when I was thinking about talking with you about this, as, you know, how far do we go? Because I’ve got notes in my brain on metabolic syndrome, peripheral neuropathy, Alzheimer’s disease, multiple sclerosis. There’s a whole heap of different avenues we can go down to. Some of these studies are, you know, I’m just thinking of one now. It’s 625 people over 10 years, for metabolic syndrome, type 2 diabetes. There’s, you know, a lot of different avenues, and some of this sometimes comes down to actual dose. So, think about the application: sports, gout, other health conditions. It comes down to dose. Now, typically the doses we use here in Australia, because we are limited with the TGA, so, Therapeutic Goods Administration, on doses of vitamin K2. So, appropriate doses, I’d say, is based on the age group. So, typically, adults are 90 to 180 micrograms per day, based on the research, like the Knapen study and a lot of other researchers, based on that dosage, 900 to 180 micrograms…sorry. Ninety, not 900. Ninety, please. Ninety to 180 micrograms per day.

Children 10 to 18, because clinically, they’re seen as children still up until the age of 18, that’s 90 micrograms per day, and children less than 10 years of age is 45 micrograms per day. So, I’ll talk about safety avenues in a moment, because that’s something that you and I have discussed over coffee, about, you know, safety of nutrients, and nutritional medicine, etc. The reason why I think the doses can be too high is, it comes down to metabolism. So, it’s too much of a good thing, is a lot. So, there’s an old saying. Someone’s, what is it? Someone’s dose is someone’s healing and someone’s poison. I forget the whole phrase, but there’s a phrase of, you know, comes down to the dose of the person.

And if a lot of research is being based around this 90 to 180 micrograms in adults, that’s an area that we seem to really need to sort of focus on. And, keeping in mind, is it making the pathways work more effectively? Is it, you know, depositing calcium crystals more effectively? It’s hard to say, because I haven’t seen a lot of that toxicology data, for example, but you start to think about how things work. Are we wasting it with, you know, combining K2 and D3? No, it depends on the formula, and of course the person in front of us. And that’s one thing I always want to say, when we do podcasts and everything, is it’s always the person in front of you. What is the best dose for that person? And if they need 500 IUs of vitamin D, and 90 micrograms of K2 from your determination, that’s the dosage that they need. If they need a high dose of, you know, 1000 IUs vitamin D3, and 180 micrograms K2, that’s the dose regime and that’s where a lot of the evidence is showing. So, going hard and fast is not always the best way to do it, because, to me, it’s trying to push too much through all the time. We get excited. Some studies are very, very high-dose, and they seem to have the negative impact, because I believe the regulatory pathways are not able to function effectively, to make sure we get the best out of, you know, what it is.

Andrew: Fair call.

Dr. McEwen: A good example is water. You know, dehydration, water is very bad for you, but so is drowning. So, if you stick to the 30 mils per kilo of body weight per day, that’s the NHMRC guidelines for water, for example, or fluids, including tea, coffee, and, don’t get me started on the caffeine argument. Because when you have a coffee, you’re having caffeine with water, so therefore it repletes at the same time. If you think of it that way, that’s the guidelines based on the evidence. Then if you start drinking 5, 6, 7, 8, 9…I’ve seen some people do 10 liters of water a day, and they’re always feeling sluggish and bloated, and feeling bad. It’s over-hydration, you’re drowning the cells with fluid. You’re going against the concentration gradient, sodium/potassium pump. Nutrients, electrical impulses are not working effectively, and you can get, you know, fluid in the brain, and die of a stroke or something. Like, let’s just go serious for a second.

That’s simple, by changing the dose of water. Now, if we bring that back to a microgram molecule, such as vitamin K2, and even D3, it’s in micrograms as well as I use, these are based on doses that the body seems to accept quite well in metabolic studies, and seems to do the actions that we need. And I believe that, like with anything, if we smash the body hard, these channels that the body has, based on evolution from when were cave men and cave women, and didn’t eat every day, and you stored, you know, nutrients in the body for a period of time, and then used them as needed, we didn’t eat as much as what we do now. We have food available 24 hours a day. The body’s mechanism of metabolizing and trying to clear excess, you know, toxins, but as well as nutrients, is not as functional as what we’re pushing in. So, that’s what concerns me when I see very high doses. And some of these studies are actually good for us, because then we can see, ethically maybe not, but some high-dose studies, we can see how well something works, but also get the different thresholds. Because if the research showed that, you know, currently 180 is good, but let’s just double it to 360 micrograms is a good dose, we need to then change our guidelines in Australia to meet that. But currently, like I said, the Knapen study, and quite a lot of few studies out there, are actually showing that the dosages between 90 to 180 micrograms in adults seems to do the work.

Andrew: I take your point. And, you know, I was thinking about the risk of possibly not giving enough credence to other important signals, like inflammatory signals, for instance, in cardiovascular disease, and calcification. Brad, there was one more thing I just wanted to ask you, and that was, so, maximal dose. We should be really looking at that 180 micrograms, maybe a little bit more, depending on who’s in front of you. I get it. But not going way high. Not going too high, because of those other things. There, oh, that’s right. There was one study I looked at, and even though it was a high dose, and forgive me, I can’t remember the dose, there was no risk of extra… Let me word that correctly. There was no extra risk of thrombosis. So, it wasn’t acting like a vitamin K antagonist, if you like.

Dr. McEwen: And that’s something that we discussed, you know, recently ourselves, like talking about interactions with, you know, pharmaceutical medications, for example. And it does always come down to the person in front of you. You know, what medications are they taking? What other vitamins, minerals are they double triple-dosing on things? You know, what kind of effect are we looking at? And there are a number of studies that were out there, and one of them showed, there was a small study that showed 45 micrograms a day decrease the mean value of INR, in some patients, say. INR is related to blood coagulation. So, if you think of it that way, a lower INR means the blood clots more rapidly, and a longer or higher INR means it takes longer. So, that was one study. And that’s the one that tends to be picked up by people. There’s always certain studies. So, I always turn around and say, read the studies, read the research, you know, understand the person in front of you, look at the genetics, the biochemistry, physiology, etc. And always be careful what you read. Read the full journal article. Because the abstracts always look good, until you read the full study.

I’ll give a quick example, because I know we’re running out of time. But there’s a big omega-3 study published many, many years ago that said omega-3 was really bad, it leads to thrombosis and clots and hemorrhages, and it’ll kill you. And I’ve gone, “Wow.” I did my PhD in omega-3, so I’m freaking out now, going, “Wow, what’s going on?” So, I look into it. And this was a case study. So, I’m going, “Okay. Well, case studies are good. It’s a level of evidence that we need.” There was a man in his 70s. Okay, so he wasn’t young. He was admitted to hospital with hemorrhaging, and further investigation, which was sort of written in a very small part of the article, was he was outside, fell off a high rung of a ladder, hit the ground, knocked his head. And he was taking multiple medications, blood pressure, aspirin, warfarin, non-steroidal anti-inflammatories, and a whole heap of other things, but it was the omega-3 that caused the hemorrhage.

And I’m like, “Really?” Not the fall, not the medications, but the actual omega-3 did it. So, I get a bit triggered sometimes when I sort of read some abstracts where, you know, I believe in all research as useful, but there needs to be factual research. And that kind of thing was a bit misleading because the media picked it up and went with that omega-3 causes hemorrhaging when it can, if given the right situation. You’re a 70-year-old man who fell off a ladder and landed on your head. So, therefore, there’s gonna be other consequences of having that, let alone medications. So, always read the full paper. Look into it deeper. So, you know, after this podcast, go and read up all the material. Go and have a look, and, you know, nourish your own brain with, you know, information of biochemistry and genetics and physiology, because we’re learning more and more every day, and that’s what I love about nutritional medicine, naturopathy, and what we do, because we are learning more and more, and the greater the information coming out, it’s fantastic. And it’s just, for me, it’s very exciting, the time and place we’re at right now, with what we could do for our patients, and help each other out as well.

Andrew: Dr. Brad McEwen, thank you so much for taking us through. This is a big topic, I know. But vitamin K2, MK-7 today. It’s been great having you on. Thank you so much for joining us.

Dr. McEwen: Thank you very much for having me.

Andrew: And thank you, everyone, for joining us today. Remember, we’ll put up as many show notes as we can. There’s a lot of research here. And you can find out all of the other podcasts, of course, on the Designs for Health website. Thanks so much for joining us. I’m Andrew Whitfield-Cook. This is “Wellness by Designs.”