Latest / Wellness by Designs - Practitioner Podcast / Beyond Leaky Gut: Clinical Guidelines for Intestinal Permeability with Dr. Brad Leech

Transcript

Beyond Leaky Gut: Clinical Guidelines for Intestinal Permeability with Dr. Brad Leech · Wellness by Designs - Practitioner Podcast

• 0:03
  Speaker 1: Music.
• 0:05
  Speaker 1: This is Wellness by Designs, and I'm your host, andrew Whitfield-Cook.
• 0:19
  Speaker 1: This is Wellness by Designs, and I'm your host, andrew Whitfield-Cook.
• 0:24
  Speaker 1: Joining us today is Dr Brad Leet, a PhD nutritionist, and we'll be talking about leaky gut or intestinal hyperpermeability, and why it's not a syndrome.
• 0:37
  Speaker 1: Welcome to.
• 0:40
  Speaker 2: Wellness by Designs.
• 0:41
  Speaker 2: Brad.
• 0:41
  Speaker 2: How are you?
• 0:41
  Speaker 2: Andrew?
• 0:41
  Speaker 2: It's fantastic to be chatting with you again.
• 0:44
  Speaker 2: It's a real pleasure and almost an honour to be sharing for the very first time, and I remember a number of years ago I told you that I would give you the exclusive when it comes around to the results of my PhD.
• 0:58
  Speaker 2: So here we are and I'm ready to share what we found during the course of my PhD and I'm ready to share what we found during the course of my PhD.
• 1:08
  Speaker 1: Well, I've got to say the honour is mine, mate, because I remember you and I sitting down at the centenary of the NHAA conference in Melbourne and I didn't know you then.
• 1:18
  Speaker 1: But wow, you've exploded onto the scene and you've really helped to clarify a lot of muddy waters and things that we get dragged into because they sound nice.
• 1:31
  Speaker 1: You've cleared up a lot of this stuff and it's wonderful to see your work now being finalised as your PhD.
• 1:39
  Speaker 1: It's great to see, mate.
• 1:43
  Speaker 2: It is really nice to almost be that one to say, hey, let's clear up the murky water and provide a bit more evidence and backing and understanding to what we call our profession.
• 1:56
  Speaker 1: Now I need you to take us through a little bit of your career and sort of you know what led you to focus on leaky gut this syndrome we were taught it was called as a research subject.
• 2:13
  Speaker 1: And also, can you take us through your supervisors at Southern Cross Uni as well, please?
• 2:21
  Speaker 2: Yeah, so my PhD was at UTS Arkham with Dr Amy Steele, professor David Sibret and Dr Erica McIntyre, who are by far and I say this without any bias the best supervisors anyone could ask for.
• 2:38
  Speaker 2: You have the stats of David, you have the caring and larger picture of Amy Steele and then Erica.
• 2:47
  Speaker 2: She's just absolutely wonderful when it comes around to trying to conceptualise what we're trying to do with my PhD.
• 2:54
  Speaker 2: So, to take you a step backwards, my career started back in 2008 now it's a while now when I undertook a dance diploma in Ayurvedic medicine.
• 3:07
  Speaker 2: Now, what's quite interesting here is Ayurvedic medicine.
• 3:12
  Speaker 2: There's a lot of focus on gut health, and I even recall being an Ayurvedic practitioner telling a patient leaky gut syndrome or leaky gut it doesn't exist.
• 3:24
  Speaker 2: Well, you know, I shake my head now looking back at what I used to say, to what I say now.
• 3:31
  Speaker 2: Fast forward a few years and completed my bachelor's, and then it was my honours where this interest in intestinal permeability really started.
• 3:42
  Speaker 2: You see, I became quite fascinated with autoimmune conditions and I wanted to do my honours, and so I contacted Dr Jeanette Swoss and I was like I want to save the world, I want to find the cure for all autoimmune conditions.
• 3:59
  Speaker 2: She sits me down, she goes Brad, first of all we need Amy Steele.
• 4:04
  Speaker 2: So we bring Amy Steele into the room and they say we love your ambition, but you need to take a step back.
• 4:10
  Speaker 2: You can't find the cure for all autoimmune disease in an honours, or even a PhD or a lifetime.
• 4:18
  Speaker 2: You need to pick one small, tiny element of that topic and focus on that Now.
• 4:27
  Speaker 2: At that time I was fascinated by a researcher, the pioneer of intestinal permeability, professor Fasano.
• 4:36
  Speaker 2: I had the honours of meeting him a number of years ago and I've even got a mug with a photo of him and I on it that says Dr Brad Leach, that I got made probably about four years ago.
• 4:47
  Speaker 2: Almost that encouragement to say you know what you can do this.
• 4:52
  Speaker 2: Anyway, we digress In the meeting we looked at okay, well, what's a driving factor for autoimmune conditions?
• 5:00
  Speaker 2: And we fell onto intestinal permeability.
• 5:03
  Speaker 2: And so that's really where the focus of this permeability started.
• 5:07
  Speaker 2: Now, at the end of the day, my number one goal in all of my research is to improve how clinicians treat and manage disease in their patients.
• 5:19
  Speaker 2: So with that goal in mind, I undertook a number of different research topics to support clinicians in their treatment and assessment for intestinal permeability.
• 5:31
  Speaker 2: So really, in a very short way, that's how it kind of came about, this concept of what's now referred to as the IP guideline and my joy and fascination by intestinal permeability.
• 5:48
  Speaker 1: Well, I can see your joy always, but I have to first ask before we move on have you met Alessio yet?
• 5:55
  Speaker 1: Alessio Fasano.
• 5:58
  Speaker 2: Yes, yes, I met him in 2018 over in America and we were wearing almost matching um, he was wearing a tie and I was wearing a bow tie and they were knitted cruciate, and it is a photo I will treasure for the rest of my life.
• 6:16
  Speaker 1: I love your idiosyncrasies you wear a bow tie but you're extremely artistic.
• 6:21
  Speaker 1: I won't get off topic, but I love your personality, brad.
• 6:25
  Speaker 1: It's got so many compartments to delve into, so let's move on with the IP guideline, which you've mentioned.
• 6:32
  Speaker 1: So, from conceptualising first intestinal hyperpermeability, can we talk first about this syndrome bit?
• 6:44
  Speaker 1: Where did it come from?
• 6:45
  Speaker 1: What's the history of that wording, that phrase and like why did it take hold?
• 6:51
  Speaker 1: Because I can still remember back in, like the late 90s, hearing about it and never fully understanding, or sort of understanding the relevance of relevance of it, if you like, the practicality of it, because it was something that was there.
• 7:10
  Speaker 1: But how do you treat it?
• 7:12
  Speaker 1: Like you, you know, if you've got sinus, if you've got tiredness, if you've got this, that and the other, you've got so many causes and they're saying it's this, it's like, come on, like, where do we sit here?
• 7:23
  Speaker 2: I always had problems with that concept, that it was and and that's a great question, you see the concept of leaky gut syndrome.
• 7:32
  Speaker 2: We have debunked that and I will say to my critics, I'll say to the people who've tagged me on many social media posts to say intestinal permeability doesn't exist.
• 7:43
  Speaker 2: Here's this article from Stanford University.
• 7:46
  Speaker 2: The number of times I've been tagged in this article where they basically say leaky gut syndrome doesn't exist.
• 7:52
  Speaker 2: Now I support that.
• 7:54
  Speaker 2: There is no such thing as leaky gut syndrome, because the concept of syndrome means that there's a group of common signs and symptoms that someone can be classified as having like IBS.
• 8:06
  Speaker 2: But with intestinal permeability there's no group of symptoms that everybody presents with, so we can't classify it as a syndrome.
• 8:17
  Speaker 2: Now, in this Harvard article or was it from Stanford Either or they go on to say yes, intestinal permeability does exist.
• 8:26
  Speaker 2: I 100% support that Whereby this reaction within the gut not a condition, not a disease, but this reaction in the gut called increased intestinal permeability.
• 8:39
  Speaker 2: It's been linked with multiple different conditions gastrointestinal conditions, metabolic conditions, autoimmune conditions and what the research has shown time and time again is those with intestinal permeability have got increased disease activity and severity.
• 8:56
  Speaker 2: And when you go about treating intestinal permeability with some of the interventions that we might speak about today.
• 9:04
  Speaker 2: Their disease activity and severity reduces.
• 9:14
  Speaker 2: So very interesting there that we have evidence to say that managing intestinal permeability in clinical practice has a profound impact on how our patients are feeling and presenting.
• 9:24
  Speaker 1: Can I ask something?
• 9:25
  Speaker 1: Just to clear something up in my mind.
• 9:27
  Speaker 1: My understanding is that intestinal permeability is a normal part of life.
• 9:33
  Speaker 1: We send out dendritic cells from the gut into the lumen to sample things normally, but it's intestinal hyperpermeability that's the issue.
• 9:42
  Speaker 1: Am I correct?
• 9:43
  Speaker 2: not yes, that's correct.
• 9:45
  Speaker 2: So we can have intestinal permeability.
• 9:48
  Speaker 2: Everyone has that, you know.
• 9:49
  Speaker 2: It fluctuates with age, it fluctuates with um different times of the day, but it's when there's ongoing, low grade, chronic, increased intestinal permeability, that's when it becomes a problem, right so do we know a level?
• 10:08
  Speaker 1: do we have that sort of data yet to say this is an acceptable range?
• 10:13
  Speaker 1: I go, I know we've got to go into measurement and assessment then, but do we have that parameter yet?
• 10:20
  Speaker 2: andrew, you are opening up a can of worms.
• 10:23
  Speaker 2: And when I was in the early stages of the PhD I looked at this can of worms and I said, no, this is way too big, way too difficult, I'm not going there.
• 10:34
  Speaker 2: But very briefly, what I can mention here is every lab, every method of assessment is different, and that individual method of assessment needs to be validated.
• 10:49
  Speaker 2: So we know, for example, stool zonulin can be or is an accurate marker for intestinal permeability when it's actively being stimulated.
• 10:59
  Speaker 2: Now that result, or that level pathology marker within the stool, that's been validated in a number of different settings and a number of different pathologies.
• 11:09
  Speaker 2: And then you've also got the lactulose-menotol test.
• 11:12
  Speaker 2: Now every research article will have a different cutoff threshold when looking at the ratio between lactulose and menotol.
• 11:21
  Speaker 2: So you can't collectively form a consensus because each process the amount of water patients drink, the amount of lactulose and menotol they take, how long they collect urine for is all different.
• 11:35
  Speaker 2: So it needs to be internally validated.
• 11:38
  Speaker 2: Once we have that internal validation, then it can be an indication of intestinal permeability.
• 11:47
  Speaker 1: Do we have any surrogate markers which we might use, not the actual things that we ingest, but other things that might be indicative of some issue with the gut, like, for instance, a raised ESR or a C-reactive protein or high sensitivity crp?
• 12:07
  Speaker 2: you know it's interesting um, one of our studies found that there was a quite a strong correlation between intestinal permeability, the markers zonulin, and inflammatory markers such as crp, esr and calprot.
• 12:21
  Speaker 2: But it's the chicken or the egg what comes first?
• 12:25
  Speaker 2: Is it the inflammation driving the permeability or is it the permeability driving the inflammation?
• 12:30
  Speaker 2: So it's quite difficult to determine exactly which one came first.
• 12:36
  Speaker 2: Other markers there are markers out there.
• 12:40
  Speaker 2: Let's take lipopolysaccharides.
• 12:43
  Speaker 2: That's quite a utilised marker in research to evaluate the end result of intestinal permeability.
• 12:53
  Speaker 2: So we know if there's intestinal permeability then there can be an uptake of lipopolysaccharides, lps, into the bloodstream.
• 13:02
  Speaker 2: We don't have a blood pathology marker available in clinical practice just yet, but there's a number of bacteria that we know that produce LPS and measuring that in the stool can provide us with a bit more indications as to could there be a intestinal permeability in Doris patients.
• 13:25
  Speaker 2: Does that make sense?
• 13:27
  Speaker 1: Yeah, yeah it does.
• 13:28
  Speaker 1: But I'm glad you say number of bacteria.
• 13:31
  Speaker 1: I was always very uncomfortable when they said, yeah, it's a fragment basically of the cell wall of E coli and I thought, what only E coli I have a problem with these?
• 13:44
  Speaker 1: Switch mentalities.
• 13:48
  Speaker 2: There's multiple other bacteria Now I can't recite all of them off by heart, but there's multiple I want to say about 30 or 40 different bacteria that can produce LPS, and so it's another way that we can collectively look at permeability.
• 14:05
  Speaker 2: Although it's not a validated marker, it can give us an indication whether or not our patient may have intestinal permeability.
• 14:16
  Speaker 1: Now we've said that you've written a guideline.
• 14:18
  Speaker 1: I've actually got it up on the other screen here and I've got to say it's so enlightening, but like it really seriously is enlightening because and challenging I've got to say for me, because things that I thought, yep, that's got merit.
• 14:31
  Speaker 1: It seems like the evidence isn't there for these things.
• 14:36
  Speaker 1: So we really have to pull our heads in and say, okay, how do we manage this?
• 14:40
  Speaker 1: And indeed, are we treating the leaky gut or are we treating the condition which the patient presents in front of us with and the leaky gut just happens to get better as we're moving along.
• 14:53
  Speaker 1: So I guess, to start treatment guideline or a practice guideline.
• 14:59
  Speaker 1: What is a practice guideline?
• 15:01
  Speaker 1: What's the term for it?
• 15:04
  Speaker 2: It's a clinical practice guideline.
• 15:07
  Speaker 2: It's a systematically developed statement that includes recommendations with the intention to optimise patient care by assisting practitioners like you and I naturopaths, nutritionists, doctors, pharmacists in their decision making.
• 15:24
  Speaker 2: Naturopaths, nutritionists, doctors, pharmacists in their decision making.
• 15:29
  Speaker 2: So a clinical practice guideline is required to be based on published evidence, so research, rather than my opinion alone or anyone else's opinion.
• 15:37
  Speaker 2: These guidelines are designed to support clinicians in their decision making for the diagnosis and even the management of any particular area, from cancers to cardiovascular disease to intestinal permeability.
• 15:53
  Speaker 2: They are actually considered one of the best ways that we can present evidence-based recommendations to the clinicians while actually reducing any inappropriate care.
• 16:06
  Speaker 2: Something to note here is the recommendations are not intended to supersede clinical judgment.
• 16:16
  Speaker 2: Clinicians are always advised to consider the patient who's in front of them first and foremost before actually following the recommendations in any guidelines.
• 16:28
  Speaker 2: Recommendations in the guidelines are there to support and guide clinicians, not to do the job of a clinician.
• 16:37
  Speaker 2: Something to note here is you can have clinical practice guidelines which are published and published in peer review articles and disseminated to healthcare practitioners, but sometimes very small percentage of the time.
• 16:54
  Speaker 2: These days some of the older guidelines.
• 16:56
  Speaker 2: They actually lack structure, and so it's really important when developing a guideline that there is a clear structure to follow.
• 17:05
  Speaker 2: Now we are so lucky here in Australia because we have the NHMRC Now.
• 17:11
  Speaker 2: The NHMRC in 2009 and then updated in 2017 and 2021, they produced the NHMRC guidelines a set of guidelines that guideline developers like myself and other researchers can actually follow to ensure that they create non-biased, accurate, clinically relevant recommendations for clinicians.
• 17:39
  Speaker 2: Something I'll note here is a few listeners will be like oh, I don't know what a clinical practice guideline is, or I've never used a clinical practice guideline.
• 17:52
  Speaker 2: Now, andrew, I know your background is in nursing, so you'll be like well, this is.
• 17:56
  Speaker 2: This is very common in a hospital-based setting.
• 17:59
  Speaker 2: So, um, gps, nurses, integr medicine practitioners they rely on clinical practice guidelines, but naturopaths and nutritionists they don't necessarily rely on these guidelines.
• 18:15
  Speaker 2: Now, there could be a number of factors why clinicians are not utilising guidelines.
• 18:22
  Speaker 2: I believe it's because clinicians naturopaths, nutritionists, herbalists they're not actually involved in guideline development and thereby their views and values and perspectives and even how they treat conditions aren't considered.
• 18:40
  Speaker 2: Because, let's face it, guidelines on average will take a million dollars to produce and five years of somebody, full time with a team to develop them.
• 18:51
  Speaker 2: I developed my guideline for a lot less than a million dollars, but that was because it was my entire focus and, let's face it, I didn't have a life outside of this guideline.
• 19:06
  Speaker 2: I get off track.
• 19:06
  Speaker 2: So, really, when it comes around to guideline development, we actually want naturopaths, nutritionists, members of associations to actually partake in guideline development and actually they are our stakeholders.
• 19:23
  Speaker 2: And so let's take the IP guideline for an example.
• 19:27
  Speaker 2: We ensured that we had patients and educators, clinicians, major associations that we have, pathology companies, supplement companies all involved in the guideline to ensure that what I was producing, what my team was producing, was relevant to not just the patient and clinician but also to our whole profession.
• 19:51
  Speaker 2: So that basically summarises what a clinical practice guideline is.
• 19:59
  Speaker 1: Well, can you take us through, then, just some of the key points of the guidelines, because, like one of the ones that's important to me, I consult in a pharmacy situation part time and that is the use of probiotics on long term, with long term NSAID use, and now previously, you know, many years ago we actually favoured this with the use of certain probiotics, but looking at the evidence here, it seems like it's very shaky ground to use a probiotic alone.
• 20:28
  Speaker 1: Can you take us through the importance of cherry picking certain things and how, as naturopaths, it actually falls into naturopathic practice in a much easier way?
• 20:41
  Speaker 2: Yeah.
• 20:41
  Speaker 2: So to answer that question, I think we actually need to take a step back and actually understand how I developed the intestinal permeability guideline, because I know a lot of clinicians out there will be like Brad, don't go talking about the methods on how you develop this guideline, just tell me what are the recommendations and how should I follow them.
• 21:04
  Speaker 2: Just tell me what are the recommendations and how should I follow them.
• 21:09
  Speaker 2: But it's so important to actually understand how recommendations are developed because I've told multiple patients hey, this is the recommendation, just like the recommendation that you've said about probiotics and NSAIDs, and their response is well, hold on, what about this intervention?
• 21:24
  Speaker 2: Or why did you write it like that?
• 21:27
  Speaker 2: So, to use recommendations in any guideline and especially let's take the IP guideline it's actually important to consider, well, what went into actually developing the intestinal permeability guideline.
• 21:42
  Speaker 2: So do you mind if I just mention very briefly those steps developing the intestinal permeability guideline?
• 21:46
  Speaker 2: So do you mind if I just mention very briefly those steps that I undertook to ensure that our listeners can understand?
• 21:52
  Speaker 2: Yep, and fantastic, because I know that you've already opened up the guideline.
• 21:58
  Speaker 2: You've looked at it, I've got the guideline for those watching.
• 22:02
  Speaker 2: I have the guideline in my hand For those listening, just imagine I'm holding the Bible for intestinal permeability, so it's very precious, all right.
• 22:15
  Speaker 2: So, quite broadly speaking, there were five major phases that we actually undertook to develop the IP guideline.
• 22:22
  Speaker 2: We assessed the patients, so we did a consumer survey.
• 22:27
  Speaker 2: We looked at the literature quite extensively, we drafted the recommendations, so in total there were 38 recommendations.
• 22:35
  Speaker 2: We also got feedback from stakeholders and then after that we were left with these final recommendations that you, as the clinicians, can actually read up, read up on and get a better understanding of how to treat intestinal permeability.
• 22:50
  Speaker 2: So, quite briefly, the consumer survey we wanted to ensure that the recommendations that we were developing were going to be appropriate for the patient rather than just focusing on the evidence.
• 23:05
  Speaker 2: There's no point developing a recommendation that that clinicians or patients don't want to follow.
• 23:13
  Speaker 2: So we know this.
• 23:15
  Speaker 2: With pharmaceuticals, we asked 589 patients what are the types of interventions you want to use to treat intestinal permeability?
• 23:27
  Speaker 2: Now, only 11% said pharmaceuticals, where 90% said I want natural supplements, probiotics, prebiotics, vitamins, minerals, and that was even the same for healthcare practitioners.
• 23:41
  Speaker 2: So with that in mind, we undertook, let's say, the most comprehensive review of the literature that has ever taken place when it comes around to possible treatments for intestinal permeability.
• 23:56
  Speaker 2: Now, when I say comprehensive, I'm talking over 10,000 articles I independently read and looked at.
• 24:05
  Speaker 2: That was a very sad time in my life.
• 24:08
  Speaker 2: It was a very focused time in my life.
• 24:14
  Speaker 2: I was doing 60, 70 hours a week in a little box at UTS just reading articles.
• 24:22
  Speaker 2: Anyway, with these articles there's a lot of studies that we actually excluded, for very good reason.
• 24:29
  Speaker 2: We know that intestinal permeability evolves over a lifetime and that the results of the IP guideline we want them to be focused on adults, so we actually excluded children-based studies.
• 24:46
  Speaker 2: The other one to consider is we excluded studies that looked at critically ill patients.
• 24:50
  Speaker 2: Believe it or not, I want to say about 30%, maybe even 40% of the recommendations or the treatments that have been investigated for intestinal permeability have been on critically ill patients Sepsis, sepsis, exactly.
• 25:10
  Speaker 2: When I say critically ill, I'm talking end of life.
• 25:12
  Speaker 2: When I say critically ill, I'm talking end of life, burn injuries, kidney disease.
• 25:16
  Speaker 2: What we know is that is a very different type of intestinal personality than what you and I will see in clinical practice.
• 25:24
  Speaker 2: So we need to exclude it.
• 25:26
  Speaker 2: Does that make sense?
• 25:28
  Speaker 2: Absolutely.
• 25:30
  Speaker 2: So after we looked at all the research, we developed these recommendations.
• 25:36
  Speaker 2: So we wanted to ensure that the developed recommendations were applicable to healthcare practitioners and also our patients.
• 25:45
  Speaker 2: So, based on all of the previous research we looked at, we funneled down all the articles and said let's focus on the main areas that clinicians are going to use.
• 25:56
  Speaker 2: They were the pre and probiotics, amino acids, minerals, herbal medicine, omega-3, vitamins and colostrum, because they're the main supplemental, and also add dietary recommendations, of course, that us, as clinicians, will actually use to treat intestinal permeability.
• 26:16
  Speaker 2: So we we gathered all these articles, we pulled out all of the relevant information.
• 26:21
  Speaker 2: Now this is the point of difference we undertook something called a risk of bias assessment.
• 26:27
  Speaker 2: Now, before your eyes glaze over, andrew, sit back, relax.
• 26:31
  Speaker 2: I want to tell you the importance of a risk of bias assessment so basically it's a.
• 26:39
  Speaker 2: It's a huge process where you look at every tiny little detail of the article.
• 26:45
  Speaker 2: You read the article three, four, five times to ensure that you've that you understand what the article was about.
• 26:53
  Speaker 2: You contact the researcher for any additional information that may be missing.
• 26:58
  Speaker 2: Now let me give you an example here.
• 27:01
  Speaker 2: Sometimes not all the time, but sometimes you have studies that call themselves a RCT, a randomized control trial.
• 27:10
  Speaker 2: Now when you go through the methods you go hold on this is a clinical trial.
• 27:16
  Speaker 2: This is not a randomized trial.
• 27:19
  Speaker 2: There was no randomization behind it.
• 27:22
  Speaker 2: Because there was no randomization, there's an increased risk of bias, that the results may not actually be what they are.
• 27:29
  Speaker 2: Another classic example that could actually impact risk of bias when it comes around to these studies is now the researchers who are listening will totally understand the clinicians may go oh, I've heard of this before is the methods of analysis.
• 27:48
  Speaker 2: So we've got a number of methods of analysis intention, treat, per protocol.
• 27:53
  Speaker 2: What we know is when an article will do a per protocol, then the results are going to be more favourable.
• 28:01
  Speaker 2: But when the researchers analyse the data intention to treat, that is including everyone that dropped out or who had side effects or who didn't take the intervention.
• 28:13
  Speaker 2: In their analysis, the results are less statistically significant.
• 28:18
  Speaker 2: So that's another element at play.
• 28:20
  Speaker 2: So, as you can see, a lot's going into developing these recommendations.
• 28:25
  Speaker 2: It's not just oh, I have a clinical trial on the effectiveness on zinc, on intestinal permeability.
• 28:33
  Speaker 2: We'll make that a recommendation.
• 28:35
  Speaker 2: There is so much more that goes into grading the evidence.
• 28:39
  Speaker 2: What I find, or what we actually utilised, was something called the MHMRC grading matrix.
• 28:47
  Speaker 2: So this is a matrix consisting of five different domains to categorise all the research.
• 28:56
  Speaker 2: So these domains let me see if I can record them they are evidence-based consistency, clinical impact, generalisability and applicability.
• 29:08
  Speaker 2: So what I mean by these is evidence-based, this level.
• 29:13
  Speaker 2: Now these are graded from A to D.
• 29:16
  Speaker 2: So if you've got an A grade for evidence-based, it's going to be a systematic review of randomized controlled trials with low risk of bias, and then it progressively gets worse where it's observational studies with high risk of bias, all the way down the end.
• 29:34
  Speaker 2: What is quite cool about utilising this matrix, this NHMRC grading matrix, is it takes into consideration a number of factors Clinical impact.
• 29:46
  Speaker 2: So we know that results can be statistically significant but they're not going to be clinically relevant.
• 29:53
  Speaker 2: So if I told you to follow this extreme diet for six months.
• 29:58
  Speaker 2: It will statistically significantly reduce weight, but at the end of the six months it's only 500 grams.
• 30:06
  Speaker 2: Yes, that's statistically significant, but is it clinically relevant?
• 30:11
  Speaker 2: No, so we can determine how much of the permeability was actually changed and whether or not that was a huge improvement Exactly.
• 30:26
  Speaker 2: And the last component.
• 30:29
  Speaker 1: Sorry, you've seen this used in a negative way.
• 30:32
  Speaker 1: For instance, I remember the common conception, the common knowledge out there is from doctors, surgeons, anaesthetists is stop fish oil two weeks prior to surgery because it will increase bleeding.
• 30:46
  Speaker 1: Well, it does, but they looked at this at the Alfred and it was 200 mil, so it was statistically significant, but it was by no means clinically significant.
• 30:58
  Speaker 1: Indeed, the Alfred Hospital had them on this high-dose fish oil up until the day before surgery.
• 31:03
  Speaker 1: So you know it's a perfect example of a misnomer.
• 31:09
  Speaker 1: That's still to this day that myth is carried through.
• 31:14
  Speaker 2: And we've applied this to the results where sometimes the diet interventions were just so extreme.
• 31:21
  Speaker 2: I'm not going to be putting that in a recommendation for clinicians to suggest, because adherence is going to be very poor.
• 31:28
  Speaker 2: The other one that I'll mention here is generalizability.
• 31:34
  Speaker 2: So a lot of studies aren't actually conducted in the Australian population.
• 31:38
  Speaker 2: You've got studies that are conducted in rural Sahara, africa or rural China.
• 31:45
  Speaker 2: Now those studies and I recall a few of them that we actually excluded they utilized whey and glutamine to reduce intestinal permeability in young children who are extremely protein deficient.
• 32:03
  Speaker 2: Yes, of course that's going to be beneficial, but can we actually apply those results to the Australian population?
• 32:10
  Speaker 2: I'm going to say no.
• 32:11
  Speaker 2: So this, this matrix.
• 32:13
  Speaker 2: I know it might sound a little confusing, but I want the listeners to understand that we have considered every possible element.
• 32:21
  Speaker 2: But the beauty is you don't need to understand or memorise anything that I've just mentioned.
• 32:29
  Speaker 2: You just need to be aware of it because at the end of the day, we produce these recommendations and we classify them as a strong recommendation, a recommendation or a consensus-based recommendation.
• 32:40
  Speaker 2: So there's three main levels that will determine.
• 32:44
  Speaker 2: Well, how strong do we believe that you should follow this recommendation and that's embedded into the, the intestinal permeability guidelines and even how we write the recommendations.
• 32:57
  Speaker 2: So when we dive into some of the recommendations, you'll see that I use terms such as offer or advise when it's a strong recommendation, so when there's systematic reviews backing up the evidence.
• 33:10
  Speaker 2: But when there's lower level of evidence, I'm going to use terms like may consider a little bit more free-flowing.
• 33:19
  Speaker 2: From there, we actually developed these recommendations and we sent them to major stakeholders.
• 33:28
  Speaker 2: Now, when I say major stakeholders, I'm talking about some of the biggest and brightest professionals in our profession.
• 33:35
  Speaker 2: I'm talking Dr Jason Hullerich, I'm talking Dr Nerala Jacobi, dr Ronald Gurdjieff, dr Michael Osiki, daini Steele, benedict Fruidman the list goes on.
• 33:50
  Speaker 2: What I'm trying to say here is these amazing, amazing stakeholders.
• 33:55
  Speaker 2: They reviewed these recommendations and they provided suggestions, a lot of suggestions where we tweaked the recommendations to ensure that when we release it to the public, this moment, right now, that clinicians will be like yes, I agree with this recommendation.
• 34:19
  Speaker 2: Just before we dive into the recommendations, andrew, I just want to take a step back and almost say how important graded recommendations are.
• 34:25
  Speaker 2: Now, something to bear in mind is we're in the era of almost too much research.
• 34:32
  Speaker 2: Now, I know that's crazy to think, but there are multiple studies in one particular area, but the studies will show different things.
• 34:43
  Speaker 2: I often see presenters even myself, and companies.
• 34:50
  Speaker 2: They will make a claim based off a single study and a lot of the times there could be fundamental problems with that study.
• 34:57
  Speaker 2: So I want to actually put a call to action out there.
• 35:02
  Speaker 2: I want to see more companies, more healthcare professionals, more presenters actually using graded recommendations.
• 35:11
  Speaker 2: Now, if that's too difficult, I want people to be utilising a risk of bias assessment, to actually not just use here's a randomised controlled trial, but to systematically look at the study and go could there be any confounding factors that impact the results?
• 35:31
  Speaker 2: Is that too much to ask for, andrew?
• 35:33
  Speaker 1: the results Is that too much to ask for Andrew?
• 35:37
  Speaker 1: It's a big ask because, like when you consider that something like 80% of orthodox medicine is without guidelines, without proper guidelines, without proper evidence, this is a big ask, this stuff, what you've done is a mammoth task.
• 35:54
  Speaker 2: I'm not talking.
• 35:55
  Speaker 2: I'm not saying that we need a clinical practice guideline for everything.
• 36:01
  Speaker 2: I'm more saying, rather than just stating, oh, here's a research article that promotes this or is associated with that disease, to take a step back and to actually make sure that we read the article to go are these results accurate?
• 36:17
  Speaker 2: Can we trust them?
• 36:18
  Speaker 1: Yeah, yeah, and I've seen that some like both ways.
• 36:23
  Speaker 1: For instance, you know, one article on one research paper on a probiotic was glowing in its results.
• 36:30
  Speaker 1: It had zero dropouts and I went meh, I smell a rat.
• 36:34
  Speaker 1: You know sorry, zero dropouts, 100% effective.
• 36:39
  Speaker 1: And then you've seen the research on this particular probiotic strange vacillate, you know, between good and you know of merit and no merit in this condition.
• 36:52
  Speaker 1: So I start to go.
• 36:54
  Speaker 1: What are we seeing?
• 36:54
  Speaker 1: What I referred to earlier and this came down to the wording that you used is clinicians may consider, not to recommend.
• 37:14
  Speaker 1: So it was really interesting with regards to a probiotic in NSAID use and a prebiotic in ncd use.
• 37:24
  Speaker 1: But wasn't there did I read this properly that when you combine them as a symbiotic, then you may consider its use?
• 37:31
  Speaker 1: And this sort of falls into the more naturopathic treatment paradigm of not one magic bullet but a whole treatment management plan?
• 37:43
  Speaker 1: Am I?
• 37:45
  Speaker 2: correct and you're absolutely correct.
• 37:48
  Speaker 2: So you've got the intestinal permeability guideline.
• 37:51
  Speaker 2: Now I'll direct your attention to table three.
• 37:55
  Speaker 2: So this is where we have listed all of the recommendations.
• 37:59
  Speaker 2: So, Andrew, you've just mentioned recommendation 2.16.
• 38:03
  Speaker 2: There are 38 different recommendations, so maybe we can discuss some of these Now.
• 38:09
  Speaker 2: I won't mention all of them because that would take way too long to pull apart, Way too long.
• 38:15
  Speaker 1: This is a read, by the way.
• 38:16
  Speaker 1: This is what are we talking about.
• 38:19
  Speaker 1: We're talking about how many pages?
• 38:23
  Speaker 2: 38 pages that's only one document, andrew.
• 38:27
  Speaker 2: There are two other documents, um, one of those documents is 80 pages, the other one is, uh, 45 pages.
• 38:34
  Speaker 2: So, um, okay, so let's dive into this a bit more.
• 38:39
  Speaker 2: Nsaids and intestinal permeability.
• 38:42
  Speaker 2: What we know is NSAIDs are used in the research to induce intestinal permeability.
• 38:49
  Speaker 2: Okay, it's a very common method.
• 38:52
  Speaker 2: Multiple studies have looked at whether or not a particular intervention is useful at mitigating intestinal permeability in those patients who have taken NSAIDs, so to induce their intestinal permeability.
• 39:07
  Speaker 2: Now, you've pointed out here I've got a section between 2.16 and 2.18, where we looked at whether or not taking probiotics, prebiotics or symbiotics had any protective effect when it came around to preventing NSAID-induced intestinal permeability.
• 39:29
  Speaker 2: What is quite interesting was we didn't set out to develop this recommendation.
• 39:34
  Speaker 2: This was more so that there was quite a lot of research here.
• 39:38
  Speaker 2: So these are evidence-based recommendations and if we're looking at the code, there's three stars.
• 39:45
  Speaker 2: So this is it's not the strongest recommendation, but it's an opinion.
• 39:51
  Speaker 2: What I want to emphasize here is, when it comes around to guideline development, we do need to consider what the research says.
• 40:00
  Speaker 2: Although if I had a patient in front of me and I had the potential of prescribing a pre, pro or symbiotic.
• 40:08
  Speaker 2: Would I give it to a patient who's got NSAID-induced intestinal permeability?
• 40:13
  Speaker 2: You know what?
• 40:14
  Speaker 2: It's not going to help.
• 40:15
  Speaker 2: Sorry, it's not going to hurt.
• 40:19
  Speaker 2: It could be beneficial, but the research on those particular strains have shown that it hasn't.
• 40:25
  Speaker 2: So I am sure that there are some strains out there that are very effective at preventing NSAID-induced intestinal permeability, but unfortunately they weren't researched and then they haven't been researched in this cohort, thereby we couldn't include them.
• 40:42
  Speaker 2: But but I know people are interested in in nsads, so I'll give you a bit of a caveat here.
• 40:50
  Speaker 2: And that is uh recommendation 3.3, and I'll read this one to you.
• 40:55
  Speaker 2: And it says clinicians should consider the use of short-term lactoferrin supplementation for the treatment of people with non-steroid anti-inflammatory drug-induced intestinal permeability.
• 41:07
  Speaker 2: So we do have something with evidence that we can recommend to our patients that has been shown to be effective at preventing NSAID-induced permeability.
• 41:20
  Speaker 1: But not colostrum.
• 41:21
  Speaker 1: There was no evidence with colostrum.
• 41:23
  Speaker 1: Nobody has looked at that on its own.
• 41:27
  Speaker 2: DR WEBSTER, that's an interesting one.
• 41:28
  Speaker 2: Unfortunately, all the research on colostrum had to be excluded, so we couldn't produce any recommendations for colostrum because we had to exclude it.
• 41:39
  Speaker 2: The vast majority, if not all, were in patients with exercise-induced permeability.
• 41:47
  Speaker 2: So that was one of our exclusion criterias, because if we looked at exercise-induced permeability, that opens up a whole other can of worms.
• 41:57
  Speaker 2: Heat shock, proteins and everything Exactly so if anyone would like to do a clinical practice guideline for exercise-induced permeability, I would be happy to provide some recommendations.
• 42:10
  Speaker 1: But yes, that is the risk, andrew FITZ, GIBBONS, if they're willing to become an absolute nerd and lock themselves in a way for a dark room in a dark room for four years, having no life um shall we give you a few more examples and true of uh recommendations that we please, please, all right.
• 42:25
  Speaker 2: So we have recommendations for alcohol use, dietary fiber, macronutrient ratios, energy intake, so that's kilojoules um gluten-free recommendations, um a number of pre-probiotics, um recommendations for glutamine, omega-3 and zinc.
• 42:45
  Speaker 2: Something I'll note here is alcohol.
• 42:49
  Speaker 2: So I will be the first to say that alcohol induces intestinal permeability.
• 42:55
  Speaker 1: I'm not afraid to say that afraid to say that.
• 42:58
  Speaker 2: But when you look at the research all the research on alcohol the effect of alcohol on intestinal permeability is short term.
• 43:08
  Speaker 2: I'm talking.
• 43:10
  Speaker 2: Participants would take one or two shots of alcohol in a setting and then measured intestinal permeability.
• 43:17
  Speaker 2: So we couldn't actually create a long-term recommendation for alcohol consumption.
• 43:24
  Speaker 2: So we actually had to fall back on the Australian Dietary Guidelines and basically say don't drink more than what the guidelines recommend, because we didn't have the evidence to say stop drinking.
• 43:36
  Speaker 2: In saying that, we produced what's called a consensus-based recommendation.
• 43:41
  Speaker 2: That's where the brainiacs of the group sat down and go okay, well, we know that alcohol can impact permeability.
• 43:50
  Speaker 2: There is research to say it does, but no long-term.
• 43:54
  Speaker 2: What can we do?
• 43:55
  Speaker 2: So we have a recommendation that people with intestinal permeability should limit or avoid alcohol consumption when they're actually treating intestinal permeability.
• 44:06
  Speaker 2: Does that make sense?
• 44:09
  Speaker 1: yeah, absolutely.
• 44:10
  Speaker 1: Um, and forgive me, I actually said the wrong thing.
• 44:14
  Speaker 1: I reread the guidelines and it says you may consider not using a symbiotic.
• 44:19
  Speaker 1: So it it's prebiotics.
• 44:21
  Speaker 1: Probiotics and synbiotics aren't really recommended for NSAID-induced intestinal hyperpermeability.
• 44:29
  Speaker 2: Wow, with the caveat that those strains, the strains that were researched, were found not to be protective.
• 44:36
  Speaker 2: That is not to say that there's other strains out there with lower levels of evidence that weren't included, that are effective, and I love my prebiotics.
• 44:46
  Speaker 2: I love my prebiotics and I want there to be an effective one, but unfortunately we didn't include any research to support that.
• 44:54
  Speaker 2: That's not to say that from the thousand other strains out there that there isn't an effective strain.
• 45:01
  Speaker 1: Yeah, I mean, you know, look how many species are we allowed to have in Australia?
• 45:06
  Speaker 1: 14?
• 45:08
  Speaker 1: Something like that, most of them based on milk, not all, but most of them.
• 45:13
  Speaker 1: We certainly don't have the joy of being able to access things like Accomantium, eosinophilia or Fecali bacteria and Proutsnitzii or any of those ones which I'm going to do a shout-out here to Clara Beltzer, who enlightened me to the merits of these microbes.
• 45:30
  Speaker 1: But you know, unfortunately at this stage we don't have the facility to use those in a therapeutic environment.
• 45:39
  Speaker 1: But one point that I make is you actually wrote this with the intention that future research will change these recommendations.
• 45:50
  Speaker 2: Of course, that is the underlying principle of a clinical practice guideline.
• 45:54
  Speaker 2: It's developed every five years because research is coming out every single day.
• 45:59
  Speaker 2: I recall, you know, finalising a recommendation and then you do one final sweep of the literature and realise, oh wait, this groundbreaking research has just been published and I actually had to get to a point where I said that's it, this is the cut-off line.
• 46:14
  Speaker 2: I can't look at any more research because I'd still be validating the research till this date.
• 46:20
  Speaker 2: So these recommendations are valid as of 2023.
• 46:25
  Speaker 2: I would like to say that the overall trend of these recommendations will stay very accurate for a number of years to come, but as clinicians, we should always take these recommendations in consideration to any new research that has been done after 2023.
• 46:46
  Speaker 1: Yeah, like I noticed, galacto-oligosaccharides isn't included in there.
• 46:50
  Speaker 1: I mean, I get it, and I'm sure that you can't.
• 46:57
  Speaker 2: Yeah, it's an interesting one where we know that GOS is very therapeutic at reducing LPS-producing bacteria, which is linked with permeability.
• 47:09
  Speaker 2: But that level of evidence to get into a clinical practice guideline it didn't meet that threshold.
• 47:19
  Speaker 1: Indirect evidence rather than direct brad.
• 47:22
  Speaker 1: There's so much to learn but I like really.
• 47:24
  Speaker 1: People really need to look at these guidelines.
• 47:27
  Speaker 1: Where can they download them?
• 47:30
  Speaker 2: yeah, so they are free to access um.
• 47:33
  Speaker 2: I'd like you to, if you can, include them in the show notes so then they're easy for people to definitely to download um.
• 47:39
  Speaker 2: If not, you can download them on my website, drbradlinchcom, and you can just download them there.
• 47:47
  Speaker 2: There are three documents here.
• 47:49
  Speaker 2: You've got what's referred to as the ip guideline.
• 47:52
  Speaker 2: That is basically the summary of all the recommendations.
• 47:57
  Speaker 2: For the gut nerds who are wanting a little more information, you can download the technical report and the guideline development process document, two documents that have a lot more information.
• 48:14
  Speaker 1: For someone who's more wanting to look at this from a research perspective rather than a bible that clinicians should be keeping up on their in their clinic room, to quickly refer to that, oh yes, I can utilize this, this treatment recommendation and forgive me, brad, I know we've sort of covered the sort of major areas, but just but just quickly, things like zinc, things like herbs, the not the well, the collagogues you could include, but also the, the antimicrobial herbs like coptis or golden seal which you know people are using, can you give us just a quick synopsis of whether they're indicated or whether there's issues with them?
• 48:56
  Speaker 1: Yes, of whether they're indicated or whether there's issues with them.
• 49:01
  Speaker 2: Yes.
• 49:01
  Speaker 2: So with zinc, there was a number of studies and it is a recommendation.
• 49:06
  Speaker 2: I'm just trying to find it here in the guidelines.
• 49:08
  Speaker 2: Here we go.
• 49:09
  Speaker 2: Recommendation 6.1, clinicians may consider using zinc supplementation in the treatment of patients with intestinal permeability.
• 49:17
  Speaker 2: As for herbal medicine, now unfortunately we couldn't actually produce any recommendations for herbal medicine.
• 49:26
  Speaker 2: Believe it or not, there isn't a lot.
• 49:29
  Speaker 2: There isn't any studies that use a validated method for the assessment of intestinal permeability in patients who are not critically ill over the age of 18, with appropriate statistical analyses.
• 49:44
  Speaker 2: I recall there's some curcumin and there are a number of herbs, but the study did not utilise a validated method to assess intestinal permeability.
• 49:55
  Speaker 2: Thereby we didn't want to include any of those articles because we wanted to ensure that the recommendations that we produced were of the utmost highest level of evidence.
• 50:08
  Speaker 1: Now I'm going to be attending a talk that you'll be doing soon, talking about or discussing the major conditions which people present with, where intestinal hyperpermeability is a major factor, where we really should be addressing this to bring the symptomatology and efficient management or effective management of these conditions down did I?
• 50:40
  Speaker 1: That's incorrect but to create effective management.
• 50:46
  Speaker 2: I believe you're referring to a presentation I'm giving on how to treat the microbiome and gut-related conditions and in that presentation it's going to be talking about what can we do to support the microbiome, to support gut-related conditions.
• 51:05
  Speaker 2: But I'll also be presenting at the NHAA conference this year down in Melbourne which I'm very excited about on a topic very dear to my heart on the impact of antimicrobial herbs on the microbiome and whether or not some antimicrobial herbs may actually have a potentially detrimental impact on our gut microbiome.
• 51:29
  Speaker 2: So I won't give too much away.
• 51:31
  Speaker 2: But, yes, I've got a number of upcoming events that I'll be talking and presenting at over the next six to five months.
• 51:38
  Speaker 1: But you're also doing.
• 51:39
  Speaker 1: This is a public talk you're doing, it's on the 23rd of February and it's one that patients can access.
• 51:46
  Speaker 1: It's a patient guide to wellness.
• 51:49
  Speaker 2: That's correct.
• 51:49
  Speaker 2: It's focused on what patients can do to improve their gut health.
• 51:55
  Speaker 1: Yeah, Wonderful stuff, Brad.
• 51:58
  Speaker 1: You and I seriously I could learn so much off you, just talking for a couple of hours and chatting, preferably over a Pinot Noir.
• 52:10
  Speaker 2: That sounds lovely, Andrew.
• 52:13
  Speaker 1: But it might transiently affect our intestinal hyperpermeability.
• 52:18
  Speaker 1: But there's so much to learn here and so much to put into little boxes.
• 52:22
  Speaker 1: But I love the way that you've done it with scientific rigor but from the point of care, from the point of actually caring for patients to make a positive impact in their lives rather than just selling them supplements going.
• 52:37
  Speaker 1: The company said it worked.
• 52:38
  Speaker 1: I love this rig and it's fantastic and it and it sees not just you but it sees natural medicine practitioners in a higher light.
• 52:47
  Speaker 1: You're improving the professionalism of our professions.
• 52:52
  Speaker 1: Um, it's, it's fanding.
• 52:54
  Speaker 1: You're improving the standing of our professions.
• 52:56
  Speaker 1: So it's wonderful work that you've done.
• 52:58
  Speaker 1: There's so much learned, so much more for us to learn here and so much more work that you have to do to make this a 90 page document.
• 53:09
  Speaker 2: Thank you, andrew, and you know I'm only one piece in the puzzle.
• 53:12
  Speaker 2: There are amazing researchers out there who are just doing incredible things for our profession.
• 53:17
  Speaker 2: I know a good friend and colleague of mine I did my honours and PhD with her Dr Jessica Bays.
• 53:24
  Speaker 2: She's now a postdoctoral research fellow at Southern Cross University and she is producing incredible work when it comes around to mental health and the diet.
• 53:34
  Speaker 2: So we're very fortunate here in Australia that we are producing so many more PhD qualified healthcare practitioners who are producing quality research to advance our profession.
• 53:50
  Speaker 2: You know we've got amazing mentors.
• 53:53
  Speaker 2: You know Dr Amy Steele, she has got so many PhD students.
• 53:56
  Speaker 2: So it's I'm only one piece of the puzzle.
• 53:59
  Speaker 2: So it's great to have the support and have so many peers who are doing so much to support our profession.
• 54:08
  Speaker 1: Thank you so much, dr Brad Leach, for joining us today and sharing your wealth of knowledge, but also your care for not just the profession but also your patients.
• 54:18
  Speaker 1: I really admire you.
• 54:18
  Speaker 1: Thanks so much for joining us on Wellness by Designs today.
• 54:20
  Speaker 1: It's my pleasure, andrew also your patients.
• 54:21
  Speaker 1: I really admire you.
• 54:21
  Speaker 1: Thanks so much for joining us on Wellness by Designs today.
• 54:23
  Speaker 2: It's my pleasure, Andrew.
• 54:24
  Speaker 2: Thank you.
• 54:26
  Speaker 1: And thank you everyone for joining us.
• 54:28
  Speaker 1: Remember you can catch up on all and I mean all of the show notes that we'll have for you today.
• 54:33
  Speaker 1: There'll be a lot and, of course, the other podcasts.
• 54:36
  Speaker 1: On the Designs for Health website, I'm Andrew Whitfield-Cook.
• 54:40
  Speaker 1: This is other podcasts on the Designs for Health website.
• 54:45
  Speaker 1: I'm Andrew Whitfield-Cook.
• 54:47
  Speaker 1: This is Wellness by Designs.