Isabelle: Absolutely. And if you don’t mind, I’ll keep calling it PEA throughout this little talk.

Andrew: Absolutely. No worries. So let’s first go through, there’s a lot of talk about PEA. It’s becoming a very popular nutrient nowadays, nutraceutical. Can you take us first through the most common benefits, the safety aspects, and indeed, a little bit about the mechanism of action of PEA, where it comes from, where it sits?

Isabelle: Yeah, absolutely. So, I understand that you actually were doing a bit of a podcast earlier with Emily Pickering about PEA, so I’ll just sort of go through a bit more of that detail, but more from a chronic pain perspective.

So, we know PEA was first formally recognized in 1957, and we know that we produce it ourselves. It is endogenously produced, and when we produce it, it’s usually made from palmitic acid in cell membranes, usually in the central nervous system. And from there, it’s only made on demand to act locally.

But in saying that, we are also able to obtain it from food sources. Things like eggs, soy products, human breast milk, tomatoes, peas. And so, we are able to get that in from outside sources. And aside from that, we’re assessing it being used in much higher doses in clinic as well. So, doses is as high as, you know, 1,200 milligrams for acute dosing.

And so, we can see from all of that, that it is incredibly safe. There aren’t many known contradictions. There aren’t any issues that we know of with withdrawal or tolerance or addictions. We know that it plays really well with other medications, and it’s got a huge array of actions.

Everything from working with pain reduction to improving anxiety. We’re now looking at how it can impact gastrointestinal function. It’s been implicated in reward behavior, so it’s got a really, really broad application base, especially if you’re in clinic. So, it’s quite lovely.

So, basically, I tell my patients, it has all of the benefits of cannabis oil, but without the, you know, unnecessary cost, without the extra-legal issues, and without the talking unicorns or munchies. So, it’s a nice way to start using something.

Andrew: Talking unicorns or munchies. How do you know about those? Anyway…

Isabelle: Well, as someone with chronic pain, I can say I have legitimately been using cannabis or under the guidance of my medical practitioners, of course.

Andrew: So, something about that, it’s an endogenous chemical. We make it and it’s used up pretty quickly. Now, we are giving it exogenously, but then we’ve got digestive processes to consider before absorption and utilization. Is there any change in its efficacy from being taken orally as appearing in the blood?

Isabelle: Well, we know that if you want to absorb PEA, especially in clinic doses, it does need to be taken in with fats, or you need to have it with dietary fats to increase absorption. Otherwise, you need to look at making it very small, so we’re looking at micronized or ultra-micronized particle sizes. And again, that’s just going to facilitate better absorption, and, of course, that will be reflected in hopefully, better outcomes.

Andrew: Gotcha. And you also mentioned our microbes. We’re obviously taking this endogenously that…I’m sorry, orally, and that means that it’s going to be interacting with our microbiota. What’s happening there? Do we get any extra benefits? Like, this is something that greatly interests me.

Isabelle: Well, that’s an area of research that’s actually happening right now, but what we do know is that because of binds to similar receptors as cannabis, and we know that can cannabis does impact the gastrointestinal system, we’re looking at how it can slow down inflammation, we’re looking at how can also impact.

So, for example, there’s one study that was showing us it does a lot in terms improving permeability for the gastrointestinal system. So, when you’re looking at chronic pain, for example, where we know there’s a lot of inflammation, and we now suspect that chronic pain and a lot of other diseases start in the microbiome as a result of low-grade chronic systemic inflammation.

It’s interesting to see how PEA can now be used to impact that. So, we’re looking at reducing gut permeability, we’re looking at how it can also impact the endocannabinoid system term in the gut.

Andrew: Right. Okay. So, like, I’m thinking more than inflammation as well. I’m thinking you mentioned hyperpermeability, but also, what about conditions that affect motility like SIBO, IBS, malabsorption syndromes, dumping syndrome, all of that sort of thing? Does it help with motility in some way?

Isabelle: It’s supposed to help to slow that actually. So, it’s slowing down motility in some cases. So, that’s actually quite interesting when you are, as you said, talking about things like IBS and Crohn’s. And when you’re also looking at those diseases, there’s also a huge factor of stress. As we all know, stress plays a role for some people with IBS and Crohn’s, and so you are looking at PEA as a way of not only addressing the symptoms but also addressing what will quite often come up with that as well.

Andrew: Right. Okay. So, next question on that is we talk about interacting with the CB1, CB2, sorry, receptors. Is there interactions with serotonin because 95% of our serotonin is made in the gut by the enterochromaffin cells? Is there any interaction there and therefore, could that perhaps be another way where it might be affecting mood, for instance, like it’s used for in anxiety?

Isabelle: Yeah, absolutely. So, there’s research coming out that’s showing us that PEA can actually amplify neurotransmitters, and it acts as a neurotransmitter in its own right as well. So, it can amplify serotonin and dopamine specifically, and we think that’s why people feel good after exercise, and we think that’s why it might be so effective for people who have low motivation.

Because it helps with those goal reward behaviors and we think that, well, again, anyone with chronic pain, you’re looking at someone who is going to be quite often unmotivated or unable to exercise because they’re in pain. So PEA provides a nice sort of way of breaking into that cycle.

Andrew: Gotcha. Okay. So, using it in clinic, now, you mentioned things like dosing up to 1,200 milligrams. Do you tend to titrate up or do you tend to do a load dose and titrate down?

Isabelle: I go high and then I bring it down. So 1,200 milligrams usually, but I will try and split that up depending on the person and depending on what they need, and then bring that down over say four to six weeks depending on how else they are improving because obviously, being a naturopath, we also look at diet as well as lifestyle factors.

Andrew: And, okay, so next question is with, you said, you know, it’s got remarkable safety profile, but we see things like, you know, they’re quite innocuous, but things like MSM, for instance, Methylsulfonylmethane. And if you dose too high on that early on, you’ll sort of overload the body’s capability to sulfate, so you get a lot of people with nausea.

Do you get any of that sort of issue? I know it’s not related to sulfation, but do you get any issues relating to overloading a system that isn’t used to it when you start with a high dose or is it just well tolerated?

Isabelle: For the most part, it is well tolerated. Although I have had some patients say that they get a bit of a tummy upset and just from personal experience, a bit of a dry mouth if I have too much as well. So, I don’t know if that’s just personal specific, but, yes, definitely a gastrointestinal upset seems to be recorded as potential side effects.

Andrew: Yeah. So, your clinical use and tell us about some research that you might be doing as well, please.

Isabelle: Okay. I don’t know how much I can say, but I will try my best. So, as part of my master’s research and you know all about this, Andrew, you’d be very familiar with, you know, with research and sometimes it’s really exciting and you wanna tell the whole world but you can’t yet.

Andrew: Yeah. So we’ve gotta warn our audience, and that is that to maintain the authenticity of research, there’s only so much a researcher is allowed to divulge during that research process or else they taint the end result. And so, there’s sort of things that have to be kept secret and then there might be an embargo period at the end before publication. So tell us what you can. How’s that?

Isabelle: Okay. All right. So, as part of my master’s research, so I’m with Southern Cross University, we have just conducted a trial looking at the use of probiotics and PEA for the treatment of symptomatic osteoarthritis, as well as stress in individuals.

Again, I can’t say too much about it because it is in the process of being analyzed, but so far I can say that the results are very much supporting the literature that we already know, which is that probiotics can affect inflammation and mood and so can PEA. So, it’s really interesting to see how that’s coming forward.

And this particular trial was actually developed and designed on the feedback from an earlier trial I did, and that was all about an end-of-one trial where we looked at the use of probiotics for the treatment of osteoarthritis pain.

So, it’s really nice because using an end-of-one trial, it’s very similar to real practice. It’s very similar in methodology to what you would do in real life. It’s just now, you’ve got clinical evidence that is on par with, you know, a really good level of evidence. So, it’s been interesting.

Andrew: Gotcha. So, just talking about the demographics of the patient population there, you said osteoarthritis. Are we talking weight-bearing joints or hands and fingers, hand and toes?

Isabelle: Honestly, it was multiple sites, so we left it open for that very reason. So, we had one patient who had osteoarthritis in the shoulder, we had one with osteoarthritis in knee, we had one with the hip, and then we had one patient who had osteoarthritis in multiple sites. And so, it was interesting to see, yeah, just how they were all able to come through.

Andrew: Am I allowed to ask if the study parameters allowed use of breakthrough medication, if there was excess pain, so use of analgesics other than PEA? Am I allowed to ask that? Tell me if I’m not.

Isabelle: You can ask but I can’t answer. I’m sorry.

Andrew: No, that’s fine. I’m just excited. I’m delving. I mean, arthritis, what is it? It said that by basically the age of 45, everybody has got some form of arthritis whether it’s affecting us or not. That’s telling not just our modern lifestyle, but I think our diet, but anyway, that’s another podcast. So, what else are we talking about with research? What other areas?

Isabelle: Well, in terms of the probiotic or the PEA or both? And even chronic pain.

Andrew: Well, the PEA with…forgive me, the probiotics was very interesting.

Isabelle: Yeah. Looking at how they can work together is really an area that’s exploding in research. I mean, just last year we had a study coming out where one company was bioengineering probiotics to then produce PEA.

So, we’re really seeing a lot of interest in that microbiome space, and how, if you can work on the microbiome or do something with the gut, that then has flow on effects and especially with PEA because being that it is part of the endocannabinoid system, it has receptor sites everywhere.

You know, whether that’s skin, tongue, reproductive organs, central nervous system, neurotransmitters. So, it’s got a lot of potential to affect a lot of areas that are impacted when someone does come in with chronic pain.

Andrew: What’s really interesting to me is how these… Now, I know we’re talking about an endogenous chemical that we are giving exogenously, but what’s really interesting to me is how we talk about feeding our microbiota. But when I looked into it in specific cases of foods like ginger, for instance, was overwhelmingly interesting to me, and that’s that they have these like nanoparticle vesicles where the genes of ginger talk to the genes of the microbes which then talk to the genes of the host as to affect an anti-inflammatory response.

So, how ginger, at least in this study, works is by this cascade. Not the ginger talking to us, it’s we’re the end vesicle, we’re the sort of the end messenger if you like. It’s the probiotics that are doing all the magic in between talking to the food.

So, I’m wondering if there might be some aspect of that, that the choice of probiotics might have some effect on how well or where the probiotics might work, for instance, in the lower…forgive me, the small intestine versus the lower intestine, the colon.

Isabelle: Yeah. Look, that’s an area that’s really interesting to me as well because when I was doing the research, especially for osteoarthritis, there was evidence showing us that like you were saying, DNA from bacteria was actually being found in synovial tissues, in the joints of people with osteoarthritis, and the DNA differed in terms of species between say osteoarthritis and say rheumatoid arthritis.

So, you’re absolutely onto something there. You know, just looking at the differences in bacteria and how you are right, it can, number one, it can translocate and number two, when it does translocate, it can then have a cascade effect. You know, how else is it talking to other body parts and how is it influencing things like inflammation or cartilage destruction or growth? It’s a really fascinating space.

Andrew: Yeah. You know, what’s going through my mind is like I’m trying to put this in a physiological sense of infection versus messages or messengers, chemical messengers. So, for instance, they’re found in CSF fluid, they’ve found DNA material. So, I’m not thinking about live bacteria, therefore, what I’m thinking about is these danger-associated molecular patterns that are found in distal locations which contain DNA or, you know, some sort of code onto whatever.

And I’m wondering if maybe when we get to a stage where there is an infection at a distal site, like, for instance, reactive arthritis, where there is an infection in that joint. Could it be that there’s been a failure of restriction of that bacteria through the system, which has been elucidated by other people with regards to how bacteria get into breast milk, but maybe there’s some sort of failure of restriction of the live bacteria getting into the joints and so it’s actually translocated?

Whereas normally, there’s a dangerous associated molecular pattern that’s allowed to elicit or, you know, be involved in inflammatory responses, but the bacteria kept out to stop an active inflammation. Research project maybe?

Isabelle: Hey, jump on board. Absolutely. You know, that is a really interesting point to consider because we know, you know, especially the immune system and the gut are very closely linked. So, yes, you know, why not?

Andrew: I’ll have Amy Steele breathing down my throat saying, “Don’t use this saying on my students.”

Isabelle: Oh, no.

Andrew: And for our audience overseas and for those who may not know, Dr. Amy Steele is one of the PhDs on board at Southern Cross Uni, taking forward students with research of which is Isabella is one. Who else is involved there, by the way?

Isabelle: Actually, I’m not under Amy Steele. I’m actually under Dr. Joanne Bradbury and Professor Sandra Grace. I just quote Amy Steele an awful lot in my research.

Andrew: Forgive me. Forgive me. You did tell me this when we were chatting earlier. You did. My apologies. My apologies. So, say the names again.

Isabelle: It’s such great field and so many great researchers, so, no.

Andrew: Yeah. So, is it Joanne Bradbury?

Isabelle: Yes. Dr. Joanne Bradbury and Professor Sandra Grace.

Andrew: Cool.

Isabelle: They have the patience of angels.

Andrew: Kudos to them and apologies. So, Isabelle, with regards to forms of PEA, now, you’ve spoken about taking it with fat, is there a form of PEA that we should be preferring to enhance or to be utilized for absorption?

Isabelle: Honestly, I work with my patients on this one, so I know it is available as capsules as well as with powder. It entirely depends on the person in front of me, and that usually helps to guide what I do and how I do it.

It depends also on their lifestyle, you know, what else they need. Sometimes it’s easy to have powders so you can blend it with other things. Other times, convenience makes a huge difference, especially if they’re busy at work. And so, you know, measuring powders might get messy or just isn’t appropriate in which case, yes, capsules are great.

And we know that there are some forms of PEA that have been designed to have better absorption and therefore faster efficacy. So, you know, if you can look at that as well as if that’s a factor, then, of course, that’s going to play a role.

Andrew: I do make the point though, that you said it’s fat soluble, it requires fat to be absorbed. And I come across this with things like curcumin, CoQ10, vitamin D, vitamin K, and that is to always have it with a fatty meal, regardless of its absorption proposed absorption mechanism. I would always prefer to have it with a meal that is going to elicit fat digestive responses like bile. Do you concur with that or do you have patients that just take it with water and go on their way?

Isabelle: Oh, look, I absolutely tell them, “Please, have it with a meal.” And also, as a buffer. You know, if we know that gastrointestinal offsets may be a side effect, then why wouldn’t you want to have it with a meal to A, improve absorption and B, potentially offset any kind of gastrointestinal ickiness that you might come across?

Andrew: Gotcha. And so, not just with these arthritis patients that you were helping in your research or hoping to help in your research but other conditions that you’ve used PEA in clinically. How long do you expect to see results after first starting PEA? Are we talking like a couple of weeks, a month, a couple of days magically? What?

Isabelle: I tell my patients to expect some kind of result within four to six weeks because that’s what the literature says, but honestly, from what other patients have told me and from what I’ve experienced, you can start to notice some change, at least some initial change, within about two weeks. So, as long as we get some sort of guide, then we know at least if we’re on the right path.

So, it’s a good place to at least give them some warning they know what to expect, and quite often they will experience some sort of change sooner if they are also changing their diet and their lifestyle. And those triggers that cause the flare-ups, especially in chronic pain. For example, stress or diet, alcohol consumption, all of that stuff.

If they know that those are triggers for them, that either A, exacerbate their pain or, you know, bring it on then, yeah, that makes a huge difference, and it can allow PEA to work much faster.

Andrew: That’s actually a brilliant point that you bring up, and that is the modifiable factors that are going to undo all of the good work that you’re trying to do naturopathically. Like for instance, you know, a low reactive diet or taking them off things in their diet and lifestyle that may be exacerbating their condition.

So, things like, for instance, smoking, alcohol, fast foods, you know, all of the inflammatory signals, but therefore, you’ve got to also look at well, what role do they play in managing the patient symptomatology versus what role PEA plays. Do you spend some time teasing that apart? Like that’s a real difficult angle.

Isabelle: It is. It really is because we know that PEA has so many broad actions. I mean, you’re looking at things like emotional processing, learning alertness. It also deals with the hunger response, and so you are also then going to be looking at is that also changing their desire to change what they eat as well because we know it’s going to impact their cravings with that, for example, you know, is that going to somehow change things along the way? So, yeah, it absolutely is something.

And I do ask my patients to just make a note of it, mental note. I don’t expect them to keep full-on health diaries and write down everything that they eat or swallow. That’s just, it might be burdensome, especially in chronic pain because then you’re just getting them to focus more on the pain, which is kind of counterproductive in some way. But it is nice to ask them to identify triggers.

Andrew: Gotcha. So, is there any change in diet or lifestyle that’s advocated like before PEA is started in this trial? Am I allowed to ask that?

Isabelle: Again, you can ask. I can’t say.

Andrew: Ah, this is killing me.

Isabelle: I’m sorry. Yeah, me too. I have to try and filter everything that I can’t say. And I’m like, “Can I say that? Probably not. Better not go there.”

Andrew: Well, at least I think I might be asking the right question, so that’s good. I don’t feel like such an idiot.

Isabelle: I’ll tell you what, when the research comes out, I will be screaming about it from the top of the mountain.

Andrew: We will wait for bated breath on that. We need to do another podcast when this is all out so that we can go, “I can now say.”

So, just going back to that dose that we were talking about at the beginning like it goes up to a maximum of 1,200 milligrams. Is any aspirations to look at dose raging studies for those people who might have a failure in their control of chronic pain? Are there any aspirations to go higher and see if there’s a higher dose that’s required in these patients?

Isabelle: It’s not something I’ve actually thought about, but now that you bring it up, it would be interesting to see because PEA has so far that we know at least such a great safety record. Absolutely, that would be interesting to have a look at. But honestly, in clinic, and I think most people who are practitioners would agree with me that you don’t really rely on just any one thing, you try and use whatever you can to help your patient.

And sometimes that’s not a case of, “Oh, let’s go higher on the dose.” It’s a case of, “What have I missed?” So, for example, if they’re so stressed or they’re not sleeping well, then I’d say, “Okay, well, let’s look at magnesium, or let’s look at L-theanine, or let’s look at something else that may improve a factor which is why they’re still in pain,” because we know sleep is hugely important for a lot of repair work.

Andrew: Salient point. Isabelle, thank you so much for taking us through this today. This is so interesting. I could sit here trying to get some information out of you about this trial because it’s acutely interesting to me that this is a patient population that is crying out for pain. There are so many patients in chronic pain who have to deal with it every time.

Isabelle: Yeah, 20%.

Andrew: Yeah. And we know they’re not getting the results that they want. They’re really crying out in pain and I just hope that your research shows patients that they have another avenue, one that’s legal, one that’s safe, and can be given to them by natural health practitioners. I just hope that this research bears out your hypothesis. That it will work. Thanks so much for taking us through this on “Wellness by Designs” today.

Isabelle: Thank you so much for having me on, Andrew. It’s been an absolute blast. Thank you.

Andrew: And thank you everyone for joining us today. I hope you got something out of that. I’m so sorry we couldn’t talk about that secret stuff. It just, it would taint the research when it’s published. And so, therefore, Isabelle, unfortunately, can’t talk about it but more next time. Of course, you can catch up on all the other podcasts and the show notes for this podcast on the “Wellness by Designs”…forgive me on the designsforhealth.com.au website. Thanks so much for joining us. I’m Andrew Whitfield-Cook