George: Sure. Pharmako is an Australian company that specializes in advanced delivery systems for ingredients that are used in the dietary supplement industry. Well, we started fairly new, so we started in 2015, but we’ve achieved quite a bit in that time. So our products are currently used by over 50 companies around the world. And we’ve also published quite a few papers, around about 15, specifically on delivery systems and dietary supplements with another five in various stages of publication. We’ve also been acknowledged with various industry awards in Australia, Asia, Europe, and America, which is showing that we’re sort of on the right track with a lot of these technologies and at the forefront of it.

Andrew: Okay. That’s really interesting. And your focus is with lipophilic delivery, correct? So we’re talking, I assume about lipophobic, constituents?

George: Yeah. Hydrophobic. Yeah, lipophobic…

Andrew: Hydrophobic. Sorry.

George: It’s all right. There’s a lot of terminology. I’ll try and not go into too much of it, but, look, lipophilic ingredients are quite interesting. They make up around about 70% of the total pool of ingredients, but they offer the most interest in terms of the conditions that they affect. So, for example, ingredients like curcumin which is a quite popular ingredient. There’s around 2000 studies being published yearly on that ingredient. Extremely hydrophobic, lipophilic ingredient. Whenever you’d read any of the studies, they all say acts on this condition, but poorly absorbed. And PEA comes into the same classes as that. So, works on quite a few inflammatory conditions but extremely poorly absorbed.

Andrew: Yeah. So I guess talking about curcumin, one of the terms which has been bastardized is the word bioavailability, rather than using the term absorption. And this has led to a lot of confusion as to the action of curcumin because, in the end, we need to be taking each of these various brands or trademarked extracts and trialling them in humans to see if they actually work in humans, because at the end that’s where the buck stops. Correct?

George: Yeah. That’s right. I always liken it to fine salt or coarse salt, you know, or rock salt, you know? So if you’re taking the same amount of salt as a finely ground powder versus a course crystal, you’re not getting the same overall effect. It is probably a bad example because salt is very well absorbed, you know, and it’s very water-soluble as well, but it all comes down to surface area. And the more surface area you have, the better absorption you can achieve with these ingredients.

Andrew: Right. So one of my, sort of, questions has always been okay, it’s a lipophilic hydrophobic ingredient. But we have bile salts, so we can digest fats. Is it not enough just to take it with food?

George: Well, what happens with your bile salts is again, they’ve only got access to the area that’s given to them. Okay. So, if you are taking a large crystal of PEA, for example, the bile salts first need to start attacking that surface to start breaking it down to then create the chylomicrons, which transfer the ingredient across the epithelial cells in the gut to then get it into the bloodstream. So, what’s important is not just putting it in your mouth and, you know, crossing your fingers that you’re absorbing it. It’s putting it in your mouth with the intention of getting it into your bloodstream first. Because that’s where it has to get to, to have an effect.

The bigger the particle, the less surface area available to your lipase, the less chylomicrons that are created, and the less absorption you have. The added problem to all of this as well is that lipophilic ingredients tend to clump. So even if you make small particles, even if you micronize them, it doesn’t mean that your body now has access to that complete surface area. Okay? Because what they do is they just clump together into bigger clumps. And then it’s up to the body to try and unclump it and absorb it. So, yeah.

Andrew: So that would obviously be a time issue when you’re talking about transit time down the human gut, where it’s gonna be absorbed, therefore, where it’s gonna act, blah, blah, blah. Do we know that about PEA, where its maximal absorption is? Forgive me. The site along the gut. Do we know that yet?

George: Look, from the pharmacokinetic study we conducted with our delivery technology, it’s getting absorbed fairly quickly. So, within an hour.

Andrew: Okay.

George: Yeah. Which means it’s getting absorbed mainly in the gut.

Andrew: Right. Okay. So that answers the question. If you don’t get it into a suitably absorption form. Forgive me, let me correct that. If you don’t get it into a suitably absorbed form, then you’ve missed the gate. The horse has bolted by the time any action can be taken upon it.

George: Yeah. You miss that window. See, the more you move down the intestine, the less acidic the conditions, which then means the more hydrophilic you need to be, to be able to get absorbed, you know? So, with a lot of these ingredients, once they miss that opportunity in the stomach, the intestine doesn’t help them much afterwards.

Andrew: Gotcha. Gotcha. So, what about combinations? Like for instance, forgive me for going off track here, but I’ve got this real love of how foods interact with different nutrients and they can help each other. Do we know anything about PEA working with any other nutrients or perhaps even probiotics? Is PEA used as a substrate maybe by probiotics, or is there anything that you can cast a light on there?

George: Yeah. We haven’t looked into it, but I’m not aware of any ingredients that would have a synergistic effect in increasing absorption, you know, of PEA. It all comes down to, when you look at PEA as a molecule and what the body uses it for, it’s created within the body. And it’s created within the body when it needs it due to a situation. Okay? So, if I were to punch you in the arm, the immediate reaction of the body would be, send some PEA to that area to null the pain, basically.

Andrew: Yeah.

George: Yeah. So, because of that, it’s naturally, it hasn’t needed to be hydrophilic or bioavailable as such, because you don’t get it from your diet. Your body makes it as it needs it.

Andrew: Right.

George: So, because of that reason, like everything in nature, it works in how it was designed to work, you know? So, because we’re not required to keep stores of PEA in our body and it makes it as it needs it, you don’t need to get any from your diet to help you along.

Andrew: Gotcha. Does it tend to therefore have a reasonably short half-life? And could also maybe a blockage in production of PEA endogenously, could that be leading or one of the reasons why there’s various dosages that are required for efficacy? Like, anywhere from 300 to, I think it was 1200, is I think that’s an actionable dose use. Is that right?

George: Yeah. Commercially, yeah, and what has been studied as well. Yeah. It’s…look, the half-life is very small. It’s probably about an hour. So although you get maximum absorption within an hour, it also starts to decline very quickly after that. Now, with a lot of these conditions, it all comes down to how much inflammation you are in basically, you know. And that’s what determines the level, the dose. So for conditions with low inflammatory situations, obviously, lower doses are required there.

For ones with higher inflammatory conditions, higher doses are needed there. We recently ran a study in Arizona, and looking at PEA and our PEA in particular with the delivery system and how it affects conditions like COVID, for example. So had some computer simulations that were showing that PEA as a molecule attaches to the spike protein of the COVID virus. But then it also attaches to the receptors of the spike protein on our cells as well. So it had this double effect, but obviously, to…

Andrew: Double blocking.

George: Yeah. Double blocking there. So, theoretically, it should stop the virus from attaching to a cell and infecting and replicating within that cell. So, we tried it on some people in Arizona, and what we saw was a lessening of the effects of COVID, in the population that was taking the Livogen plus ingredient versus the one that was taking the control. So, there was some merit in the theory, but the dose for that situation was extremely high. So again, it was around about a thousand-milligram dose. And the reason being is, you know, you’ve gotta look at viruses, you know, how many of them are, and then you also need to try and affect however many trillion cells in your body, you know, to also stop the spike protein from connecting to them. So a lot more was needed in that situation, hence, you know, the higher dose.

Andrew: Yeah. I just wanna be clear for our viewers, obviously, this is not to be construed as a treatment for COVID. We’re not saying that. You know, vastly larger studies have gotta be done. But hey, you know, there seems to be some merit in at least the theory, as you say, of double blocking that spike protein. So further work will elucidate that. Can I just ask, because of your interest in lipophilic delivery, there’s so many claims out there. You know, we’ve got liposomes. I mean, gosh, they’re from years ago. They’re from 20 odd years ago. You’ve got nanoparticles, which were newer on the market. There’s other lipophilic delivery vehicles. I remember one, I can’t remember his name. He was one of the original guys, Rutolo Bruce. Bruce Rutolo?

George: Right.

Andrew: I think Garth Nicolson has done some work with glycerophosphates. Can you take us through to unwind this confusion that I have about, sort of, where they sit, what’s their usefulness?

George: Right, right. Okay. All right. They’re all useful…

Andrew: In just three hours.

George: …in different situations. Yeah. So, it’s a bit of an arsenal and you use parts of the arsenal depending on the situation, you know? So, look, if I was to look at it from a point of view of what…well, how we see the world. Okay. So, you’ve to start with you, you’ve got the macro aspect. Okay. And then the macro aspect basically is everything you see daily, and even down to the smaller level, you know, down to the millimetre level sort of thing, where a magnifying glass can help you along. You’ve then got the micro world. Okay? So say in the micro world, you go past the millimetre stage and you go into the micron stage. And to get a better view of that world, you need a microscope. Okay.

Then we go a bit further. So we go into the nano realm. Visible wavelength of light is nonexistent in that realm, you know? So, you need things like scanning electron microscopes to be able to view anything in that world. Now, the smaller you get, theoretically, the better absorption you achieve. Okay. But to move from the micro to the nano, you need to have ingredients that dissolve in something, and that something needs to be pleasant for a human to take or an animal to take, you know, so it can’t be anything toxic. The problem you’ve got with substances like PEA is they don’t dissolve in anything. Okay, when I say dissolve, it’s different to disperse. Okay?

So, when we’re talking about dissolving something, we’re talking about free molecules of that substance being freely available in a solvent of some sort, whether it’s water, alcohol, whatever the substrate is. Now, PEA just doesn’t dissolve in anything that’s friendly to people. Okay. So, trying to make something that would work in the nano world, so a liposome, for example, is extremely difficult if not impossible for PEA. But what you can do with PEA, is you can make it work in the micro-world. Okay. So, what we can do there is get it to disperse in water. Okay. And by dispersing it in water, you are now increasing its surface area, which then is allowing the body to have access to as much surface as it possibly can, and get it absorbed basically. Yeah. So…

Andrew: Gotcha.

George: So yeah, so liposomes are fantastic. They’re not for everything. And they do take a lot of energy to create. Okay. So, they’re a very energy-intense system to make. And even when you do make them, a lot of your active is not encapsulated by the liposomal structure. Okay. So, a lot of the active is in the solvent that you use to dissolve it, which is hanging around the liposome.

Andrew: Oh, hanging around it.

George: Yeah. Yeah. Yeah. Not only inside it, it’s outside it as well. But what liposomes offer is they offer a very targeted delivery system. So, liposomes will get through most membranes. Okay. Because you’re talking about structures that are down the 50-nanometer area. Okay. When you look at a typical cell, a typical cell might be 20 microns, so 20 or 50 microns. So this thing is, is a thousand times smaller than a cell. Okay. But what it does do is it mimics the membrane of a cell. So the body doesn’t see it as a foreign substance. And because of that, it takes it up quite easily and readily into the cell. Okay. So, it’s very targeted to deliver something straight into a cell.

With things like swollen micelles, you know, or micelles in general that are self-emulsifying structures. So you’re not talking about expending any energy there to make this substance. Okay. Or make this structure. So, you’ve made a clever mixture of ingredients, which as soon as it touches water, it instantaneously creates a micelles structure. Okay. In that situation…

Andrew: Wow.

George: Yeah. In that situation, 100% of the active is enclosed within the micelles. Okay. And because it’s lipophilic, the internal structure of the micell is lipophilic, that’s where it tends to go. But they’re not as targeted. Okay. So, it doesn’t mimic the cell wall. It is a nice circular spherical structure. But it can be made to be more targeted by other means. And what I mean by that is by using ultrasound or magnetic waves or heat. So, you know, taking the substance with micelles and then hitting a particular area with magnets makes the micell fall apart in that area and release the payload, basically. Okay?

Andrew: Ah, okay.

George: That’s getting really tricky. That’s getting super-advanced delivery systems.

Andrew: But that’s kind of like along the lines of using, you know, chemotherapy and heating certain areas of the body, like for instance, the tumour area. And we’re talking orthodox medicine, not the whole body thermotherapy. So yeah, they sort of pinpoint or target an area for thermal exhortation in the hope that the chemotherapy will have a greater effect in that area. Is that the way it sort of works?

George: Well, you can piggyback onto that. So, you can deliver a substance, a toxic substance to the cancer, enclosed in a micell, deliver it to that area. And on the proviso that when you hit it with the radiation of whatever sort, it falls apart and releases the payload. So, it’s very, very precise and very directed in that situation.

Andrew: Wow.

George: Yeah, yeah. It’s next-gen stuff, but they’re working on it in various universities around the world.

Andrew: Gotcha.

George: But yeah, look, micelles are great. They’re interesting. Not as small as the liposomes, a proper micell is, but the self-emulsifying ones are generally larger. But nonetheless, they still do a good job of delivering ingredients too, within the blood plasma. Okay.

Andrew: Right.

George: So let’s talk about that a little bit because you mentioned inflammation previously. And you’ve done some work with PEA and quercetin, right?

George: Yep.

Andrew: Can you tell us a little bit about why you chose quercetin rather than say curcumin or I mean, possibly is a reason, you know, there’s so many anti-inflammatory agents that could have been chosen, EPA DHA, for instance.

George: Yeah. Yeah. Look we’ve done a lot of work on all of those things, you know. So omega 3 has definitely done quite a bit of work there. So we’re able to increase their absorption sixfold and, you know, have an effect on omega 3 index and omega 6 ratios as well. Very, very positively have an effect even to the point where we compared it to Krill-Oil, which is supposed to have, you know, its own natural increased absorption and a very good effect on all those parameters. But if you add some of our delivery technology to it, it makes it so much better again. So, look, probably the single ingredient we’ve studied the most has been curcumin, but PEA comes a very, very close second.

We’ve had, I’d say, about five studies published on our Levagen plus ingredient across multiple conditions. So, looking at it from a joint pain point of view to delayed onset muscle soreness in athletes, to sleep and how it affects sleep patterns and, yeah, yeah. Alertness on awakening, you know, those sort of situations. And then also, as I was talking about the COVID study, you know, so in other unorthodox situations as well.

Andrew: Yeah. Yeah. What about neurologious or neurological type conditions?

George: That’s where it’s supposed to shine. So, when you read up about PEA, it’s more so in neuralgia that it has an effect rather than in chronic inflammation in general, you know. So, something acute. So you suffer something quickly, you need to address it, you take your PEA, you address the situation. And then it all subsides. It all goes away. Whereas if you’ve got a chronic condition, like, like arthritis, for example, you know, I’d be going for the curcumin. Yeah. It’s something you need to take.

Andrew: Are we talking about different inflammatory signals here?

George: Yeah. Yeah. You’re talking about numbing the pain versus treating the pain. You know, so that’s the difference. Think of it as, as ibuprofen, you know, you’ve got pain for whatever reason, you take your ibuprofen, the pain goes away, but as soon as you stop taking ibuprofen, the pain comes back again. You know?

Andrew: Yeah.

George: But if it’s a headache, for example, which is self-limiting in its own right, that’s the one that works. PEA does job there, you know? Yeah…

Andrew: So things like headaches, migraines, sleep you said. Arthritis is gonna be an interesting one, but DOMS, that’s a real interesting one.

George: Yeah, yeah. Yeah. And it definitely had an effect in that area as well, so. But it had more an effect on markers that were not related to inflammation. So, we ran a study in DOMS using both the Livogen plus the PEA and HydroCurc, the curcumin. And then we were, you know, looking at swelling. Swelling of the muscle tissue, nF kappa beta, CRP, you know, etc., etc. It was just a whole raft of markers. What we noticed was that the curcumin was having more an effect on the traditional inflammatory markers. The PEA was having an effect on the other measures that weren’t related to inflammation as such, you know?

Andrew: Wow.

George: So, yeah, it was interesting in that, overall it reduced the delayed onset muscle soreness by a third, basically. So, where the control was still affected after day three, after the exercise, the treated groups were able to go back to training after the second day.

Andrew: Right. So forgive me because I’m thinking about the timeline of DOM. So I’m thinking about you do the exercise, day one is okay. Day two is murder.

George: Yeah.

Andrew: So you’re saying that people can return to exercise on day two?

George: After day two. Yeah. After day two.

Andrew: Wow.

George: Yeah.

Andrew: So you still gotta go through hell?

George: Well, it’s reduced hell.

Andrew: Yeah. So, is that why you would use it commonly with other anti-inflammatory agents? Like you, you know, you’ve done some work on curcumin and there’s cosetin and, you know, we’ve mentioned a few of the others.

George: Yeah. And look, there’s about 300 inflammatory markers that we know about. Okay. So, so God knows how many there really are. Now, all of these substances are having an effect on multiple inflammatory markers, but there’s nothing there that’s doing everything, you know? So, it’s basically what condition are you trying to affect, what inflammatory markers are having an effect on that condition, and then trying to find the suitable ingredient that can affect those inflammatory markers? So from our aspect, we chose curcumin because it’s got such a high spectrum of inflammatory markers that that has an effect. Yeah.

Andrew: Yeah. So with regards to PEA though, relevant dosages, do you tend to use loading dosages and then pull down to get a really quick effect, get over it, get over DOMS, and get on with your day? Or do you tend to use the standard, sort of, medium-dose or whatever, like 300, 600 milligrams?

George: Yeah. Sorry. In the DOMS study that’s exactly what we did. So, it was a high single dose just before the exercise. And the exercise was quite brutal, you know. So yeah, it was basically, leg presses to 80% of their capacity and then added more until they burnt out basically until they couldn’t do one. So, it was quite brutal. It was designed to induce DOMS. Let’s put it that way.

Andrew: Yeah. Yeah. Yeah. And what dose did you use?

George: In that particular one, it wasn’t high. It was only 170 milligrams of Levagen plus. Yeah, which translates to roughly about 150 milligrams of PEA.

Andrew: Right. No, that’s not high at all.

George: Yeah. Yeah. And then they…

Andrew: I was thinking like 2 or 100.

George: No, no, no, no, no. The only one that we did anywhere close to that number was the serious condition. Yeah, the COVID study. Yeah, that was the only one. Yeah.

Andrew: Gotcha.

George: Even with…so we did a comparative study and I can give you a quick heads up, but I can’t go into too much detail because it hasn’t been published yet. But we put head to head Livogen plus versus ibuprofen in mild to severe headaches. And the good news is, the Livogen plus reduced the amount of the time that it took to get back to normal, so to say. So where ibuprofen was taking two hours to get rid of the serious headache, Livogen plus was taking about 90 minutes. So…

Andrew: Wow.

George: …significantly less. Yeah.

Andrew: Oh, that’s highly significant. Yeah. And, so along with that…

George: For its natural substance…

Andrew: Yeah. So along with that, you know, people taking ibuprofen regularly you’ve got issues of gastric irritation, such and such. What sort of safety issues are there with PEA? Anything?

George: Yeah. There’s none of those issues. So, when you look at the dropouts, you know, with most of these studies, you get an indication of how many of them are real and how many are, you know, figments of people’s imagination. We don’t see any serious conditions, adverse effects with the Livogen plus.

Andrew: Right:

George: On the contrary, yeah, ibuprofen has many, many issues.

Andrew: Yeah, yeah.

George: Yeah.

Andrew: I think it’s is it 1100 people per year? I’m gonna get this wrong. It’s either 1100, 1600 people per year in the U.S. die from correctly prescribed NSAIDs. But you know what? I’m just wondering about, I know you’re talking about it’s better in the acute sort of situations. But even in more chronic situations, if you could take, let’s say, the two ibuprofen as a loading dose with say one Livogen plus then as the box instructs, you take one or two subsequent of the ibuprofen. Imagine if they can keep on just one. Imagine the lessening of the gut insult from just having one, halving that dose of NSAIDs. A 50% reduction of NSAIDs and taking PEA to take the rest of that load off the headache and things like that. That’s quite dramatic.

George: Yeah. We’re working on a study at the moment that’s doing exactly that. So, halving the dose of ibuprofen and replacing it with Livogen plus, and seeing how it affects it. So initial results are quite promising in that it has a better effect, the combo has a better effect than the ibuprofen on its own.

Andrew: Now, George, I know that sometimes you publish studies and, you know, that depending on the publishing house, you’ve gotta pay for the actual paper, and sometimes that’s scores of dollars. But where can people find out more? Can we get all of your research please to put up on the Designs for Health website?

George: Yeah, absolutely. Yeah. Look, most of it’s in the public domain, so I can direct you to the links. Yeah. Not a problem.

Andrew: That’s great. That’s wonderful. George, thanks so much for taking us through PEA today. It’s really interesting stuff that you’re doing with different drug delivery systems. Very interesting stuff indeed.

George: Thank you. Thank you, Andrew.

Andrew: And thank you everyone for joining us today on “Wellness by Designs”. Remember, you can catch up on all of the other podcasts and indeed the show notes to this podcast and George’s research on the Designs for Health website. I’m Andrew Whitfield-Cook. This is “Wellness by Designs”.