Dr. Gabrielle Fundaro, CISSN, CHC, is a Renaissance Periodization consultant, Monash low-FODMAP certified and ISSN-certified sport nutritionist, and ACE-certified health coach. Dr. Fundaro combines her knowledge of nutrition and motivational interviewing techniques to promote intrinsic motivation and behavior change in clients to facilitate long-term weight management and healthy lifestyles. In this episode, Gabrielle and I give a true "state of the union" about the human microbiome and how to truly optimize our gut health.
Connect w/ Gabrielle @vitaminphd and her website. www.vitaminphdnutrition.com
Jade: [01:17] Welcome to the show everybody. Today, I have Dr. Gabrielle Fundaro hanging out with me. You can reach her at vitaminphd on Instagram. Vitaminphd, @vitaminphd on Instagram and on her website vitaminphnutrition.com. Please go visit her, tell her you listened to the show, show her some love. Let me give you a little bit of background on the discussion today before I turn it over to the actual interview. We talked about an awful lot of things, and mainly what you’re going to get out of this discussion is a very good understanding about the current state of research, and the misunderstandings that many of us in the natural medicine space, in the health coaching space, in the medicine space have related to the gut microbiome, and probiotics, and all these things. We get a very good understanding that the research in this area is far from clear, it is very much in the gray zone, and at best, people are misleading themselves and others when they are teaching some of this stuff, and at worst, they’re getting it completely wrong. So, we get a really good sort of state of the union in terms of where we are with this science in this particular interview. Also, just a heads up, at the beginning of this, we had a little bit of technical difficulty, so it may seem a little disjointed here in the beginning since we basically cut out some of the bad sort of signal that was coming through, and then we get into it from there. It ends up being an amazing discussion. I learned a ton. I hope you do as well, and without further ado, Dr. Gabrielle Fundaro.
[02:58] Welcome to the show everybody! I’ve got Gabrielle Fundaro, PhD in the house with me today, and I’m super excited that she’s here. She is an expert in many realms, but mainly focuses on gut related dysfunction, and especially metabolic endotoxemia, which is something you’ve heard me sort of talk about before, and she’s here to educate us all on this. We’re lucky when we get to have someone of such a big knowledge base, have a PhD on the show to kind of help us figure this out. So, Gabrielle, welcome! Thank you so much for being here and spending time with us.
Gabrielle: [03:31] Thank you so much for having me, and for that gracious introduction! I appreciate that.
Jade: [03:37] Well, let’s actually – I want to just clue everybody in to how you and I met. It’s kind of a funny story – and this is the Next Level Human podcast – and I just want to clue you guys into this because, for me, it’s all about being sort of a next level human. And by that, what I define that as someone who is all about growth, someone who can see their dysfunctions, someone who wants to learn. So, part of what happened with me and Gabrielle is I posted something, I forget what is now, something on – something that was related to gut – and this is her area of expertise. And she came in and said something that I made an assumption and was kind of triggered by, so I kind of went to my base level self and her and I had this little tiff or disagreement online, and we’re kind of going back and forth. Then, I sort of recognized that I was being a little bit ridiculous, and I actually had seen she had sent me a previous message that was very, very sweet, and then we started talking and I was just like you know what, I really just want to have you on because I want you to educate us. So, it was one of these moments where I kind of caught myself being sort of in this base level, making assumptions that weren’t her intention at all, and ended up learning an awful lot in the process. So then, and now we get to kind of learn from her. I think the lesson there is, sort of like this podcast being the Next Level Human podcast, try not to make assumptions when people are really trying to help you with their expertise. That’s one of the things, and I’m really glad that she kind of forgave me for sort of the way I was with her, and then is now here helping educate us. So, it was a funny thing, but one of the things that we sort of began to talk about, and one of the things we were discussing, we were discussing this idea about the difference between me being a clinician and you being a researcher, and I know you kind of do both, and I dabble in a little bit as well; I’m a clinician researcher, but I’ve never done PhD work like you. I would like for you to just help us understand sort of the difference of this. We’re getting hit – a lot of us – with science constantly, and there’s a lot of, what I would say, armchair researchers, and I kind of fall into that category for someone standing on your end of the equation where you’re like hey, I’ve done PhD work in this, I am the person who’s actually in the lab, I’ve done that work, I have that knowledge base. Help us understand how you make sense of this, and just walk us through how when you’re looking out there in the world of social media and you’re seeing people talk about science how you’re evaluating this stuff, and how we can be better.
Gabrielle: [06:04] Oh, I just love that you shared that story, and I’m totally with you on using feedback as a tool for growth. That’s part of how I started following you on Instagram was looking at your posts on personal development and growth. So, to answer your question on sort of… I guess the difference between experiences as a PhD vs. experiences as a clinician-
Jade: [06:34] Ok, just jumping in real quick guys to let you know this is where Gabrielle and I lost some of our signal, and we’re going to pick back up and you’ll see me give a little bit of background on what she was talking about, and then things are smooth from there. Let’s get back to it.
[06:48] Ok, so you were essentially talking about the idea that there’s a problem with looking at some of these inflammatory markers, especially LPS, that what might be statistically significant might not be physiologically relevant, and whether or not these tests can actually tell us much when we’ll see someone who we know is in sepsis having low markers when they should be “high,” and also other people having very high markers and not having symptomology. Am I getting correct sort of what you’re alluding to there?
Gabrielle: [07:23] Yes, exactly. Yep.
Jade: [07:24] So, if that’s the case, and we have this sort of issue where people like me, who aren’t as well versed in the research as you, and then people who have no research background are sort of reading these things and also trying to – someone like myself – trying to be effective in the clinic, and also thinking that they’re seeing changes. What is the best way to kind of make sense of this? If that’s the case, how much should we be relying on this research, and how much should we be looking at sort of our clinical observations? Because one of the things I know is a very big deal and a lot of people talk about it is this idea of evidence-based medicine. And sometimes when I hear that, I kind of go yeah, evidence-based medicine is all about looking at the research, but it also takes into account clinical experience and the individual sitting in front of you. So, do you have any suggestions about how to help with this conundrum? Like, how to deal with this. How should we be looking at these research studies, especially on these inflammatory compounds and things like that? And to what degree can we trust our clinical judgement vs. the science?
Gabrielle: [08:30] I think one thing would be to fall back on, you know, even if we have a single randomized controlled trial that is really compelling, one thing I always want to do to doublecheck myself is look for the presence of systematic reviews or meta analyses. Not to say that those are infallible, but at least they give us a bigger picture, and obviously, an evaluation of the strength of the evidence. So, things like those two, or Cochrane reviews, which are another form. That’s really what I utilize to form the basis of my recommendations.
Jade: [09:11] Ok. And what Gabrielle is referring to, just for those of you who don’t know, she’s essentially referring to reviews and meta analyses, and Cochrane is an organization that essentially specializes in doing these reviews and meta analyses, or sort of studies of studies. So, she’s sort of alluding to – and make sure I get this correct, Gabrielle – but she’s sort of alluding to this idea that one study in and of itself doesn’t mean much, especially if we have some of these confounding factors that she’s already spoken about. What she does is she goes and actually looks and says are there multiple studies and is there a leaning towards sort of a finding where we can start to make some assumptions based on multiple studies. Usually, the people who do these reviews and meta analyses are looking for only well done studies, so they’re kind of often times tossing out the ones that aren’t that well done, and they’re looking for sort of trying to make an understanding of the current body of evidence. Am I getting that right, Gabrielle?
Gabrielle: [10:06] Yeah, absolutely. Then, we can actually start to determine the strength of relationships between two factors. So, we can look at an analysis of their correlation, so our being – if our’s is -1 – so we can have a negative correlation; that means when one thing increases another thing decreases. We can have 0 which means there’s no relationship at all, or we can have a positive 1, which means when one thing happens the other thing always happens. But of course, correlation is not causation, so that means we can’t determine cause and effect, but we can at least determine whether two things tend to happen at the same time. And we can look at other analyses as well that tell us the magnitude of effect that one might have on another; so, when one thing goes up, how much does the other thing go up or down. From there, we can determine ok, what’s the correlation, or what’s the relationship, and then how strong or how weak is it. That way we can determine whether, for example – and from this, we can also look at things like absolute vs. relative risk – if your absolute risk for something is very low, then the relative risk is going to be a fraction of that low number. And so, we can, I think, reduce I think some of the fear around some of these potential issues by saying ok, so your chance of ‘x’ is low, and when we look at relative risk for you personally, it’s even lower than low, so here are your potential interventions, here is the potential strength of the effect each one might have. Then, we allow them to make decisions based on all of that information. Where I think the fitness industry is headed, unfortunately, is more in the direction of you are significantly broken and these are all the things that you have to do to fix whatever is wrong with you, and especially in the area of gut health, because it’s so new and there’s so much misinformation and misunderstanding that people are, I think, excessively concerned about what might be problematic in their gut health and how that affects their metabolic health and weight and things like that. Really, the reality is we know very little because it’s an incredibly complex system. The best we can do is to examine these correlations using these secondary analyses and then make kind of educated guesses, which I think is part of, you know, that’s part of evidence-based practice. We try to use the best evidence available and then our clinical practice, as well as, obviously, the experience of the individual. But, I think the other caveat there is that we certainly need to validate their experience, but also provide education. So, if they come to us with, perhaps, a limiting belief, that we can empower them with the correct information, and then they can move on from there.
Jade: [13:08] Yeah, I love that this is where you’ve gone because, for me, I really wanted – and I know for some of you listening to this, you know, listen to Gabrielle speak, you’re talking to a PhD who’s been doing this – so some of it may get a little bit beyond you, but I think the point that she’s driving home, and that I was hoping to kind of discuss with her, is this idea that if you are someone – you know, it’s interesting, the less a person knows, the more stubbornly they know it. That’s a quote by Osho, and I think this is especially the case in when we’re looking at health and fitness information. We have sort of the lay public, who reads an article by a blogger who’s maybe a health coach and has very little understanding in this vs. clinicians who are sort of doing this work but aren’t really trained researchers vs. a researcher, which is kind of why I wanted to have Gabrielle on here. What’s she’s essentially saying to us is that, especially in this area of gut health, which we have her here, so I’m going help kind of tease out what her best guesses are, but especially in the area of gut health and is it relates to probiotics, there’s so much more that we don’t know, but that’s not really what you’re being told out in the public. You know, it’s basically like we’ve got this all figured out, the gut is the seed of everything, just take some probiotics, take some digestive enzymes, you’re going to be just great, you won’t ever get another autoimmune condition, etc., etc. I think that’s what Gabrielle was reacting to with my post, and I think that’s what a lot of us are reacting to on the other side. And there’s also a lot of fear around that, and a lot of misinformation, so I wanted her to come on and say ok, given the state of the science and that there are a lot of these issues in the science that many of us are not aware of, and given the state of especially gut health, things like metabolic endotoxemia, probiotics, what can we know, Gabrielle? Walk us through like the things that if you’re just like ok guys, I know that you’re all interested in this field of gut health, this is what I’ve done my PhD in, I also realize that you want tangible sort of clinical tools to use, and we don’t necessarily maybe have a lot of that because the science is so new, but walk us through what you actually feel like are some of the things that we can begin teasing out and actually using, in clinical practice and for individuals.
Gabrielle: [15:25] Well, I’ll start at sort of just the basics of the gut microbiome and sort of what we know about it. I think – and I’ll do this from the vein of trying to bust some myths concisely – I think we have to address the idea of a healthy gut. So, differentiating that from what… the healthy gut being, you know, is it the gut microbiome or is it the anatomy and physiology of the gastrointestinal tract. We can look at the gut microbiome or the gut microbiota, so those are the microorganisms, and the microbiome is all the genetic material in the gut. We can sequence that, and from the genetic material available, generally identify who’s there; so, what microbes are present. Where do we run into some issues? Well, if we do that from individuals in different parts of the world, healthy controls will actually be significantly different. We don’t have one specific profile of a healthy gut. We have been able to identify some keystone species that have coevolved with humans for so long that they should probably be there, and we have a general idea that dysbiosis could be either an increase of pathogens, or a decrease in beneficial bacteria, or some combination of both. But dysbiosis is literally just a difference from a healthy control, but since healthy controls all look different, you can start to see where it becomes very problematic to try to define dysbiosis. Likewise, we haven’t been able to create a causative link between dysbiosis and any disease. So, to say something like we would remodel the gut in some way is, I think, a bit of an overstep in what we’re actually capable of doing, because we haven’t even really been able to determine what’s the “best gut.” Likewise, when you look at longitudinal studies, we find that even if we have dietary interventions, physical activity interventions, even in the presence of a disease, that about 60-80% of the microbes present remain stable throughout life. From the initiation of, you know, introduction of solid foods, all the way up to elderly adulthood, things are very stable. That’s actually a good thing. We want to have a resilient sort of ecosystem of the gut. So, are we going to be able to make huge changes to the entire population there? Arguably no. Well, what are some of the lifestyle factors that we find correlate with enhanced microbial diversity and gut barrier function? Looking at how well do the cells in the immune system of the gut help to defend against pathogens. It really comes down to the basics of… physical activity, fruit and vegetable intake, and maintaining a normal body weight or a body weight that is associated with reduced risk of disease. So, it’s really nothing groundbreaking at this point, we’ve just been able to identify that bacteria seem to be able to ferment fibers to beneficial short-chain fatty acids, so we need sufficient fiber in the diet. Generally speaking, we’ve found that a high fat diet often results in some form of dysbiosis, and we can talk about that, you know, its relationship to metabolic endotoxemia, although it’s not always consistent. But aside from that, there’s really very little that we can say conclusively. You know, on the topic of probiotics, yes, some strains do seem to consistently confer benefits to specific pathologies, but even that is quite limited. And part of the problem with probiotics research is this lack of reproducibility. So we have one study that shows something and then another study can’t reproduce it. I think it just comes back to – and you might agree with this too – coming back to the basics and looking at your physical activity habits, your habitual diet, and what are you doing to prevent sort of the chronic diseases that we see in westernized society. I sort of have called these the diseases of luxury. You know, when we can be sedentary and have easy access to really highly energy-dense foods, rather than trying to like fix something, because we don’t necessarily know that it’s broken.
Jade: [20:03] Yeah, you know, I love that – I know some people this idea, that they’re like oh my God, c’mon Gabrielle, that’s not sexy enough for me – but I love that, because in a sense, for me, in a sense – I am a naturopathic physician. That’s my background. Part of the reason I went that direction is because I recognized that they were not teaching lifestyle medicine in traditional medical schools. I was sort of brought up as a personal trainer, I was steeped in nutrition, and I remember looking at the curriculum for a traditional – the MD degree – and was appalled that none of this was being done. There was no training and exercise, there was no training and nutrition, there really was no training and mindset, and that’s all the stuff that I thought I would be getting in medical school. However, having gone the naturopathic route, I also tend to see some of the exact same mistakes being made in the naturopathic realm. Rather than giving a drug, it’s just hey, take a digestive enzyme or a probiotic, or something like that, and they’re still not doing these basics that you’re talking about, right? I will say I agree with you 1000% that often times when people make those simple changes, most of the need for other things sort of goes out the window, and it’s sort of taken care of, especially for the vast majority of the general population. So, I love that you’re saying that, and everyone listening, I would essentially say, you know, when you think about what is being said here, we have to, I think, be very careful about the sexiness of – just because we’re maybe anti-drugs and surgery, which I certainly am not. There’s a time and a place for that – doesn’t mean we should have this pro-natural medicine bias either. It’s about what works, and I think what Gabrielle is saying what works right now is we’re kind of in the wild wild west of gut health and probiotic function and the microbiota. We don’t know a whole lot, but we do know that the basics that you’ve always heard tend to work well. So, the way I’d like to follow up on that though is the following: you and I both know that clinically speaking, and certainly this is rolled over into the lay world now, where gut restoration programs are essentially all the rage, and I will also say that clinically speaking, they’re one of the most effective things I have ever found in my clinical practice to address sort of these broad spectrum sort of… conditions that really you can’t put a handle on. So, it looks like there might be some skin rashes, and maybe some autoimmunity, or maybe something going on, or some fatigue, but you can’t really put your finger on it; and then you essentially institute these so-called gut restoration programs, and people seem to do very well on them. Then, it begs the question, and I’ll get your take on this, but it always has begged the question to me, is it simply that we clean up the diet, and/or is it all the supplements that we’re using - the digestive enzymes, the probiotics, the glutamine, things like that – or is it a combination of both? I’m guessing you’re going to say Jade, we don’t know, but we might have our guess there. But what is your take on that, and do you see that clinically as well? And to what degree can people sort of take some of this advice and move forward with it?
Gabrielle: [23:28] So, I think we have to be careful about looking at correlation vs. causation and that the current absence of evidence doesn’t mean there’s evidence of absence. However, we do in some cases have evidence of the absence of effect for some of these things. Being somewhat familiar with the 4R approach, and I’ve read some of the books about gut restoration, I think first addressing the idea that we can sort of wipe things out and repopulate them, especially in any kind of selective way, that really doesn’t not appear to be the case. One of the big examples I think about is when people talk about like a yeast cleanse of some sort; so, trying to eradicate yeast. Well, there are beneficial strains of yeast that we actually do need. They’re considered to be commensal in the gut, and one of them is a probiotic as well. So, S. Boulardii, and when we talk about candida cleanse, you really wouldn’t want to eradicate that. And because we don’t have the ability to create any causative links between any one microbe and the outcome of the disease, we have to be very careful about making claims about wanting to eradicate any of these microbes. You can think about it like eradicating mosquitos. They are irritating, they carry disease, but if we were to eradicate mosquitos, it would have a deleterious effect on the entire ecosystem. So, we have to keep in mind that these bacteria and other microorganisms are interacting with one another as well as ourselves. I think we should have to be transparent and say yes, diet, and physical activity, and various other things can influence the microbiome in ways that we don’t fully understand, and we cannot, without a huge dose of antibiotics, make a big dent in who’s there. And we probably wouldn’t want to either because that would put us at risk for disease if we were to completely kind of wipe things out and then repopulate them. In terms of repopulating, you know, when we’re using things like probiotics, we also have to keep in mind the limitations of how we’re determining what has been done there. If we’re using just fecal samples to determine whether a probiotic has sort of enriched the gut, well, regardless of whether a probiotic actually enriches – kind of takes up residence in the gut – we’ll see enrichment in fecal samples, because a fecal microbiome is actually significantly different from what we see in the colon or small intestine or stomach. And it is further different from what we would see in the lumen vs. the mucosa of the intestine. So, we also have to keep in mind when we’re talking about the gut microbiome, we actually have multiple sort of subcommunities within that population. Now, when we do something like an elimination diet, I actually recommend, if I work with folks who have symptoms of IBS, one of the most effective interventions thus far appears to be the low-FODMAP process that was developed by Monash University. Now, they’re not making claims about making changes to the microbiome, it really just comes down to temporarily removing some of the fermentable fibers and carbohydrates that can cause the production of gas, or they’re osmotically active, so they pull a lot of water into the gut; temporarily removing those and then reintroducing them in a systematic way so that each individual can determine the type and the amount of those carbohydrates that they can personally handle. That could have an effect on the microbiome. But once again, because we don’t have a causative link between changes in the microbiome and disease outcome, we can’t say that that’s what causing, or preventing or improving any of these symptoms. It just so happens that those two things happen at the same time.
[27:26] With some of the specific supplements, glutamine being one, there are actually a number of meta analyses and systematic reviews on glutamine; and I’ve read about this a lot, because it was something that was popular in athletes, and unfortunately, there’s really no strong evidence to show that glutamine – although, as part of an amino acid, yes, it is necessary – but glutamine supplementation specifically doesn’t appear to have any significant outcome, or result in any significant outcomes. Whether we’re talking about gut barrier function or intestinal permeability, even in people who are hospitalized for serious illness, the only consistent finding is that it’s associated with shorter hospital stays, but that doesn’t necessarily mean that it’s doing anything, because it’s certainly not having physical effects. Looking at the effects of dietary enzymes, digestive enzymes – so, this is another thing I’ve written about a little bit in a piece that I’m collaborating on, actually for greens powders, because digestive enzymes are popular in greens powders. There are pharmaceutical grade enteric coated digestive enzymes that can help with some issues, like if a person has exocrine pancreatic insufficiency, so not producing digestive enzymes. Those seem to be the most effective forms. If we’re looking at an over-the-counter digestive enzyme, one, it would have to have an enteric coating so that it could survive transit through the acidic environment of the stomach. These enzymes, because they’re proteins, are active in specific pH ranges. It would also have to be given at an appropriate dose in the ratio to the amount of the offending food that a person is eating. So, not to say that they’re completely ineffective. It does appear that lactase, and I want to say it’s galactosidase, those seem to be somewhat effective with small amounts of either dairy or foods containing that fiber, like beans. Those can be somewhat effective in alleviating symptoms. But something like a probiotic, we have to understand when we’re looking at the effects of probiotics, they’re strain specific. So, a strain is a subspecies, it’s extremely specific. It’s like looking at the difference between a dingo and a dog, and if we’re saying like, everyone needs to have a house pet, and just pick a canid, it doesn’t matter, well, you could end up with something that would be potentially very dangerous to you. You don’t want to have a dingo, you want to have dog. Likewise, the effects also appear to be very disease specific, so there’s not just a kitchen sink probiotic that would work well for everyone. Because we run into those issues of heterogeneity between studies and a lack of replicability, we have to be very careful about what we’re recommending for whom, also keeping in mind that there are risks associated with probiotic supplementation. So, they’re not just this sort of panacea that works for everyone without risk because it’s a natural thing. I think that’s where we sort of run into some issues with this, is that we assume that something is natural that it’s not going to be harmful, and that’s really not the case. I hope that gives kind of a big picture. That’s my rundown of that approach. Not to say that elimination diets don’t work, they can, but we just have to be transparent about what they’re doing. Or that digestive enzymes don’t work; they can, but the application, just like probiotics, is extremely limited. We have to be transparent about the effects that they might have.
Jade: [31:02] Yeah. I think if I’m hearing you correctly, and all of us can kind of learn from your education, I’ll just kind of paraphrase back -and I’m doing this just so you can be like yeah, Jade, you got it, or no, you missed this part, or no, you completely misunderstood me – but it sounds like essentially what you’re saying is look, we’re in a huge gray zone whenever we start to make definitive sort of statements about the effectiveness about things like digestive enzymes, probiotics, any kind of so-called gut supplement. We’re kind of in this really big gray zone because the science just doesn’t support the vast majority of the claims, and there’s not much we can pull out of the science to essentially say hey, this is exactly what’s going on. It feels like that’s the first thing you’re saying. Then, the second thing you’re saying is that in some cases, there’s very little data at all for using some of these things, and it does seem you’re opening up the door a little bit to say hey, look, certainly you have seen clinically that some people can benefit from especially sort of allergy elimination programs and things like that, but this may not be related to these supplements at all. It may just simply be related to things like FODMAPs and these highly fermentable fibers, and other things of that nature. So, when we look at gut function, we essentially go back then to your original statement, which is saying that there are things that are maybe not be sexy but we should really be looking at that we actually know seem to be beneficial. Am I getting that essentially right, and I think you’re not saying that, you know, we shouldn’t ever kind of experiment with these things, but that when we do, we could be doing harm, and we also need to be aware that they don’t actually, in the research, don’t actually have a high sort of probability of being effective; at least, the studies don’t show that as of yet.
Gabrielle: [33:00] Yes, exactly. And I would even say that, you know, I think some of it maybe comes down to the nomenclature. When we’re talking about things like food allergies vs. intolerances vs. sensitivities.
Jade: [33:13] Sensitivities. Yeah, exactly.
Gabrielle: [33:16] I can expand on that a little bit because that’s sort of one of my other… it’s sort of another area that kind of puts up red flags.
Jade: [33:23] Let’s do that because it is. Even I find myself, you know, talking about food allergy when it’s not actually what we’re meaning. Then, there’s also do these other things actually exist. So yeah, walk us through the whole idea behind what is a food allergy, what’s a food sensitivity if we can say what it is, what’s a food intolerance, etc. IgGs, IgMs, go as deep as you want.
Gabrielle: [33:44] So, the way that I like to define it sort of simply is that a food intolerance is enzyme mediated. That means that we don’t have the digestive enzyme needed to break that food down. It may be due to a genetic mutation, so we’re supposed to make the enzyme but we don’t; and in some cases, it’s just because we’re human and no humans make the digestive enzyme to break down some of these fibers, for example. That’s why they’re so beneficial to the gut bacteria. We can’t break them down, so they pass to our colon and the bacteria use them instead. So, that’s a food intolerance. Lactose intolerance, we lack the lactase enzyme to break down lactose, and because we can’t break it down, it remains in the GI tract where it can be fermented and cause gas and bloating. So, enzyme mediated is an intolerance. An allergy is immune mediated. Now, that means that our immune system is reacting to that product and exerting some response to it. It’s creating sort of these inflammatory cytokines and other compounds that can result in potentially life-threatening anaphylaxis, or maybe just hives and things that are - perhaps dermatitis; so, we can have an allergic response. Now, we can have an IgE mediated allergy, so that’s a specific type of antibody, or we can also have non-IgE mediated allergies. That means that IgE antibody is not involved, but it still is considered an allergic response. Now, we can be screened for IgE mediated allergies and non-IgE mediated allergies, but that is not necessarily a diagnosis. You would have to go to an immunologist or an allergist to get one of these screenings done, and then you would really go through a subsequent series of tests. You could do something like an oral tolerance test and you would determine whether an allergy actually exists, because even just an IgE response is not necessarily indicative of a full-blown allergy. Quite often people are sort of getting these false-positive results thinking that they can’t eat this food, and in fact, they’re going to be fine eating that food, they just had a minor IgE response. Just like your immune system is saying like oh, this is a foreign thing, maybe this shouldn’t be here, should we be on high alert maybe. Now, the area that is creating sort of mass confusion at this point would be the area of food sensitivities. I will be completely clear – a food sensitivity is not a real thing. IgG food sensitivity tests are tests that identify foods you have eaten. The IgG antibody is not one that is going to be utilized in an allergic response. This is very problematic when people go to get the IgG test because they then receive a giant list of foods that they have eaten at some point in time. Now, you could do that for free with just a dietary recall, but people then use that as sort of an intervention, or they eliminate all of those foods and perhaps they feel better, and that’s great. It’s definitely – that’s what we want, right? We want our clients to feel better. But the problem is they have just coincidentally removed some food that may have been just a FODMAP, just a fermentable fiber issue. So, it wasn’t that they were having any sort of response to it really, it was just they probably could’ve eaten a little bit less of it and not had gas. Or they may have removed a food that they had, perhaps, a non-IgE mediated allergy to… but then they apply causation to that. They think that oh, these foods were causing my issues, I don’t eat them anymore, now I feel better, and perhaps they never eat those foods again, and we know that that could certainly cause issues. If a person significantly reduces the variability of their diet, that could result in reduced energy intake, and perhaps they lose weight; and if that’s what they were intending upon, ok, that’s kind of a cool side effect, but at the same time, now they have significantly reduced dietary variety. What I have seen folks coming to me that are really trying to figure out their GI issues, you know, they spent the time and the money on these tests and perhaps they still don’t feel good, or perhaps they feel better but they’re eating only 6 different foods now, so they have not been empowered by that information. That information has now sort of changed them to this extremely restrictive diet and these limiting beliefs about what they can or cannot eat. I think that’s a very important differentiation and one fault that I find with some practitioners that are utilizing these tests without maybe understanding exactly what they’re measuring or not. But the IgG food sensitivity test is one that I’ve seen that’s just really problematic at this point, and it is not testing for an allergy, and it is not testing for an enzyme deficiency. Literally, the IgG antibody is just a recognition antibody.
Jade: [39:03] Yeah, you know, I have a funny story about that I’ll tell you that you may or may not laugh about – but it’s funny, clinically, as a naturopathic physician, we utilize these things a lot, and especially in my early career, I was running a ton of these things. What I’ve found was, you know, one minute, the patient would come in and be lit up like a Christmas tree on this thing. If anyone’s ever seen these panels, they’ll basically like rank them in sort of red, yellow, and green, so when you’re in the yellow, you got kind of a mild sort of reaction, and if you’re in the red, you’re kind of having a severe IgG reaction. What would happen is I would look at this and I would be like, I would run these things repeatedly, which is – I kind of have that mind where I’m like, let me see how this changes with my interventions. And what you would find is really no rhyme or reason. One thing would pop up, it would be there in a severe, then the next thing you know, it would be gone and something else would be there, and I was chasing this all around. The only thing that I got clinically from this, eventually I just started seeing the degree to which – and I want to get your take on this – but the only thing I started – I stopped running them, by the way, a long time ago – but the only thing that I could do clinically with that is that the degree to which I saw lots of yellows and reds was the degree to which I could see severity in whatever symptom that they were having; but the foods didn’t seem to be related, and they seemed to be exactly the things that they were eating the most of. So, if I had them cut out one thing, and then they started eating more of another thing, that would then show up in the red next time I ran this test. I started seeing it as not very useful, but I did start to see it – and I want to throw this out and see what you think about this – I started seeing this as sort of this is indicative, perhaps, of increased gut permeability, and maybe that’s what’s happening here, because the only rhyme or reason that I could see for all these sort of markers showing up was that. But I want to get kind of your take on that and see what you think. I have since stopped running these things because, to your point, I didn’t really find them clinically useful. They were more confusing than anything else, but that is one thing that at least, in my mind, and I saw sort of like there was a correlation. Again, to your point, correlation and causation are two different things, but there always seemed to be a correlation that the more than they had red and yellow on those tests was correlated with the more severity of whatever they were dealing with. One aside to this that I’ve seen clinically over and over and over again is the idea of a gluten sort of sensitivity, actual gluten intolerance, associated with Hashimoto’s thyroiditis, and actually eliminating gluten, even when they’re not pure Celiac, and then seeing these enzymes, these antibodies rather, go to near zero. Now, of course something like Hashimoto’s is a disease, for those of you that don’t know, that naturally waxes and wanes. Many people speculate why that’s the case - is it related to certain dietary elements or is it just related to the way the immune system functions. But, do you have any comment on that and how you would think about that? Do you think, yeah Jade, maybe there’s something there, or no, I think they’re completely useless, and any comment on sort of the correlation of certain dietary elements like gluten with certain disease conditions like Hashimoto’s.
Gabrielle: [42:28] I think that gets to one common assumption that people make, that enhanced intestinal permeability would result in some symptomology… and that’s actually not the case. There are no symptoms of intestinal permeability that where we can say you have GI distress, or you have eczema, or you have fatigue, and that’s a symptom of enhanced intestinal permeability, which is really interesting. You would actually kind of think oh, if a person has increased intestinal permeability that they would have something wrong, diarrhea or bloating or something, but that actually does not appear to be the case.
Jade: [43:13] Especially when we kind of see – just as an aside – one of the things that was always interesting to me about intestinal permeability is the fact that exercise, which is a very healthy thing that we all kind of want to do, increases gut permeability. We certainly don’t see, you know, traditionally, people breaking out in rashes post exercise, so it’s just an interesting point that you’re making.
Gabrielle: [43:34] Right. Well, and with exercise, that’s sort of a special case. It can increase intestinal permeability, and it actually can result – when we’re looking at ultra-endurance exercise, that’s also associated with elevated plasma endotoxin levels, and also associated with gastrointestinal distress; so, it seems like those things can all happen at the same time, but not necessarily, and I think that it really highlights that we don’t, again, have a causative link between intestinal permeability and gastrointestinal distress or even various disease states. So, we do have… data – we have meta analyses that have looked at some of the most potent risk factors for intestinal permeability. Not to say, again, that there’s a causative link, but it looks like individuals with BMI greater than 25, individuals with Type 2 diabetes, individuals with late stage non-alcoholic fatty liver disease, and inflammatory bowel disease, individuals with gestational diabetes, they do seem to be at increased risk of having – or increased odds I should say – of having intestinal permeability. But intestinal permeability can be measured by a variety of mechanisms, and not all of them are looking at metabolic endotoxemia. Intestinal permeability is even different from gut barrier function, because intestinal permeability we’re really just looking at how close together are the intestinal cells, whereas gut barrier function is looking at how response is the immune system to whatever is coming through the gut. So, if we want to look at something like an immune marker, potentially, of intestinal gut function, we’d want to look at IgA, so it would be yet another antibody. IgA is really specific to the gastrointestinal tract, so we could potentially look at that and then determine from that, you know, is that potentially a sign of increased intestinal permeability; perhaps, and, well, what does that actually mean clinically. Does that mean that now we do have a elevated plasma endotoxin levels? Ok, if that’s the case, is it to a point that it’s going to be problematic? Is it associated with comorbidities, and then we go from there.
Jade: [46:00] Yeah, and with some of these things, there’s definitely a chicken and egg problem here.
Gabrielle: [46:03] Yes!
Jade: [46:04] I think one of the things you’re kind of pointing out to all of us is saying, you know, listen, yeah, you have intestinal permeability and you have some of these conditions, that doesn’t mean that that caused it. It could’ve been the other way around, and we don’t yet know in the research. It sounds like that’s sort of your major caution for us. I just wanted to jump in but go ahead where you were headed.
Gabrielle: [46:25] Yeah, no, that’s exactly it. Yeah, we have this chicken/egg problem, we have these correlations. In many cases they are weak also, so that’s the other thing. It’s sort of like well, these things tend to happen about the same time, you know, half the time they both happen together. Like, oh, ok, that’s interesting, but do we act on that? I think that kind of, you know, this is reflective of the way I coach also. I really start from the basics and then I look at, you know, do we have any special considerations here? Well that, once we ticked off all the other boxes, now we can look at special considerations; but looking at something like the IgG food sensitivity test, I mean, there’s just no mechanistic explanation that links those foods to intestinal permeability. We wouldn’t have any symptoms of the intestinal permeability, and I think from there, we can fall back on what are – there’s nothing wrong with doing an elimination diet, we just have to do it in a systematic way, in a way that kind of makes sense mechanistically. Part of the reason the FODMAP process makes sense is ok, we’re taking these carbohydrates that are highly fermentable, they create gas, they are osmotically active, they pull water into the gut, so it makes sense those would cause some perceptible side effects. Then, we look at that in RCTs, in individuals with IBS who go through FODMAP vs. those who don’t, do we see some improvement in outcomes; and even that, it’s not an infallible intervention either. They approximate, I think, 40% of individuals won’t even see an improvement after going through a low FODMAP diet. But it’s one that I think is just… we know that it’s valid and it’s evidence-based, and is effectively free, versus one of those tests which are kind of really expensive and don’t tell us much. We run into the same issues when we’re doing things like these GI map tests where we’re doing sort of an analysis of who’s there, who’s in your microbiome right now, that it’s sort of like doing a 23andme but for your gut. It’s interesting. It’s cool to look at. It is probably, you know, we could probably fairly easily guess what’s going to be present based on your dietary and physical activity habits. But again, it’s not something that can be used for clinical interventions because we don’t have a specific profile for this is what it should look like vs. this is what you look like, and we can’t create a causative link between any of those microbes and disease outcome. We just have to be cautious, I think, about how we’re using the tests.
Jade: [49:12] Yeah, I mean, I’m so grateful for that because, I think – if you’re listening to this – I think some people, they hear information like this and they’re like well, then everything I knew or thought I knew, I don’t like this because now what. But if you really listen to what Gabrielle is saying, I mean, these allergy elimination – “allergy elimination” diets and things like that – these are kind of the gold standard because they are, essentially, a randomized controlled trial on yourself, and you don’t have to worry about all the sort of whether these tests are working or not. You essentially bring your diet down to sort of a base level diet taking most of these things out, especially if you’re removing the FODMAPs, and then you add them back in one at a time, and you’re going to know. That, to me, is – and it sounds like to you too, Gabrielle; correct me if I’m wrong – but this is a clinically relevant, smart way, that doesn’t get into the mess of all these assumptions that we might be making by trying to translate science that is not yet complete. I think that’s sort of the first thing here. I do want to just briefly, before I let you go, and I want to be sensitive to your time, but can you kind of help us with this particular problem that I know a lot of people would ask about if I didn’t ask you. What is going on – there’s a debate now, which I find kind of funny, and I have sort of my understanding about it which I’ll share here and then I’ll let Gabrielle sort of tell me how wrong or how right I am – but there’s this idea now where we have lots of intermittent fasting, and lots of keto diets, and lots of these very low carb sort of high fat diets, and many people feel good on these things, and often times they come to me and say Jade, what have you seen clinically? And it’s funny, because I have seen both; I have seen people who start these diets and literally feel miserable, and I’ve always tried to kind of think, you know, what is actually going on there. I mean, there’s a lot – there’s blood sugar imbalance, there’s high stress hormone output whenever you take carbohydrates away. Some people are more sensitive to that stuff. But one of the other things that some people might point to is, you know, if we’re talking about something like LPS - which I know you’re going to have a field day with this, but I’ll tell you my understanding and then you can just break me down with this – but if you’re thinking about something with LPS, many people have said, right, if you have the wrong – let’s say you’re eating your standard American cafeteria diet, lots of sugars and lots of fats - and so, maybe we can say, and maybe we can’t say based on what Gabrielle says, that we’re growing some of these “negative probiotics.” Maybe. Like maybe we’re getting a lot of these gram negatives that are shedding these LPS, and LPS is lipophilic, so it likes fat, and it’s being driven into sort of our blood stream and perhaps having some of these inflammatory reactions, which is why we might wake up sort of feeling achy first thing in the morning after having, let’s say, pizza; maybe that’s going on, maybe it’s not. But what I want to ask you is to what degree do we – because there are some people that just say take out all fiber, you don’t need it, just have these very high fat diets. What I’ve seen is some people feel almost like they have the flu, beyond just… blood sugar issues and things like that. They are flu-ish, and achy, and almost like they have an infection when they move from an immediate sort of higher carb cafeteria-based diet, to this high fat diet. I have always speculated that that is the idea of you have all this LPS around, you’ve just moved your diet to 80% fat, and a lot of that’s being driven in. Is there any, you know, is there any sort of rationale that you would be like, Jade, you have a point; or are you just kind of like no, I don’t think that’s what’s going on at all, or any thoughts on that. Especially when we have people nowadays saying you don’t need any fiber at all, you should just eat all fat and protein and not any fiber. What’s your take on that, and then I’ll say thank you and let you go for the day.
Gabrielle: [53:07] Oh, this is such a good question, and we’re looking at a couple different variables here. So, are we looking at a diet that is high in fat and devoid of fiber, or are we looking at a diet that has normal fat and devoid of fiber, or high fat-high fiber, and some of these questions just haven’t been answered yet. But what you’re really getting at is the idea of metabolic endotoxemia, and that, theoretically, if we ingest a diet that is very high in fat, we may cause some deleterious changes to the microbial community that could lead to an overgrowth of bacteria that would shed off lipopolysaccharide, and we actually a couple other endotoxins as well – LTA, I want to say it’s lipoteichoic acid, and peptidoglycans. So actually, both gram negative and gram positive bacteria can shed these endotoxins, and once they enter circulation, bind to various immune receptors and cause this low-grade inflammation, this cascade of cytokines that has been implicated in overall just metabolic dysregulation; so, skeletal muscle that can’t accurately respond to increases in glucose or fatty acid availability. And this has been seen, we actually do have human data, both in short term and long term high fat feeding challenges, and in individuals with obesity and Type 2 diabetes, that they do tend to have higher circulating levels of LPS, and in some cases, higher levels of TLR4, which is what LPS binds to. Now, would we necessarily have symptoms associated with metabolic endotoxemia? That, I think, is not apparent in the literature yet, at least, not in terms of gastrointestinal symptoms or pain or things like that. And we’re looking at very low levels of inflammation, so it’s not something that we would feel like if we’re having soreness or an illness or something. So, probably part of what we’re seeing when people are switching from a carbohydrate-based diet to a ketogenic diet would be the feelings that we get when we are… have very low blood glucose, and we’ve used up all our muscle glycogen and now our liver’s just sort of pumping out glucose, we feel fatigued and foggy and kind of crummy. That could be something that’s related to the gut or not, we just really don’t know all of the mechanisms there. Now, in terms of some of the links between high fat feeding and metabolic endotoxemia with or without fiber involved, the data in humans is actually fairly limited, but we have found in rodents adding fiber to a high fat diet can be protective. Even just high caloric intake in humans is one of the – it can increase odds of having elevated LPS. And in rodents if we replace that caloric excess with carbohydrates rather than fats, we don’t see it quite as often. But again, because, you know, how I mentioned earlier where we had so many limitations with the assay that we’re using to measure LPS, it’s very difficult to determine this effect with consistency. But I think what’s consistently found is that we can’t necessarily quantify the amount of LPS, that there’s usually an increase in response to high fat feeding, whether it’s acute or chronic, and so the cutoff from one of my – where I actually did my dissertation – they actually had put out a paper in 2015 kind of talking about this, and postulated that maybe instead of looking at LPS levels, we need to look at an increase from baseline. If we have, like, a two times increase from baseline, could that potentially be considered metabolic endotoxemia, because everyone’s sort of starting in a different place. But generally speaking, I would say based on what we have from rodent data and from human data, because we do have some RCTs looking at specific dietary caloric contributions from fat, and it looks like if we’re approaching a diet that’s 40% calories from fat, that generally tends to reduce microbial diversity, and also correlate with increase plasma endotoxin levels; and if we are adding to that, a diet that’s completely devoid of fiber, well, fiber plays a number of beneficial roles, not just in creating stool bulk, but also serves as a substrate for bacterial fermentation that results in the production of some of these beneficial short chain fatty acids. Not to say that those can’t be made from amino acids, but we have to look at the amount. Is the amount that’s being made from amino acids equivalent to what we would get from fiber? I think that that sort of is another layer of potential risk if we’re having a diet that has no fiber at all. Why do people potentially feel better on it? Because, to be honest, fiber can cause some unpleasant gastrointestinal side effects and we don’t like the way that that feels. Certainly we can adjust the diet to address that issue, but having less gas or more comfortable bowel movements is not necessarily indicative of enhanced gut barrier function, microbial diversity, or intestinal permeability. Once again, there is a significant divide between symptoms vs. the physiology of the gut and the gut microbiome.
Jade: [58:57] Yeah, I just love that. You’re incredibly brilliant. Thank you so much for kind of helping us sort of understand this. And I imagine someone sitting on the other end of this and being like, ok, well, I feel like everything I thought I knew about this area of health is now been sort of exploded in sort of all these myths. I would say and submit to people that – and I’ll just get your final thoughts on this and then we can wrap up – but what I would say to that is that what we have to understand is that there will always necessarily be a gap between the art of health and fitness and the science of health and fitness, and what we can’t do along the way. I think Gabrielle has been amazing at helping us, cautioning us to do this – we can’t just make stuff up, and I think in that vein, essentially all she’s doing for us is saying listen, there are some things that we might know, most of it we don’t yet know, let’s not make things up, because if we start making things up, we go in potential directions that confuse the process and potentially could do harm to individuals. I think that’s important that we do that, both for me as a clinician, for the scientists who are out there educating individuals, and especially for the lay public. So, I think we need to take this and just say ok, we have now got a very good sort of understanding of the state of the science, right? And it doesn’t necessarily mean we can’t experiment in the clinic because often times that can inform the science, but we have to sort of understand that. I would just say for the person who is sort of now a little bit agitated, whenever we, as humans, get our biases and our dogmas and our old beliefs sort of shaken up, like probably has been done for many people for this, I would say that that’s a good thing. It’s a growth promoting thing. It’s the whole point of this podcast. But what would you say, Gabrielle, for someone who’s just kind of annoyed, maybe feeling like a little lost now in their understanding of this? What would be your sort of final take home that, for you as an educator, would just be hey look guys, here’s how you need to look at this, and here’s where I would like to leave you with my final thoughts?
Gabrielle: [01:01:12] Oh, absolutely. I really love that message, and I really appreciate you saying that, and acknowledging that people will probably be experiencing some cognitive dissonance. I would say that that is a really valuable and necessary part of learning and growing as an individual and as a practitioner. There’s a great book called The Art of Thinking Clearly, and the author talks about this idea of sort of shooting your darling; so, if there’s something you feel you adhere to very, very passionately, you should be able to argue for both sides of the debate. That way you can at least be aware of where the other person might be coming from, and really examine the issue with as much objectivity as is possible as a human. You know, we’re all humans, we’re all emotional, but I think just acknowledging that is so valuable. I really welcome people to reach out and ask questions. My whole aim, really, is just to educate and empower folks to make sure that, you know, they can avoid the individuals who want to sort of market the misinformation and misunderstanding, and to know that we can be more confident that we’re not necessarily broken and need to be fixed, and continue to grow from there.
Jade: [01:02:39] Tell us where – it’s vitaminphd, right, on Instagram. Is that where you spend a lot of your time, and where else can people find you and get your education?
Gabrielle: [01:02:50] Yeah, so vitaminphd on Instagram and Facebook. My website is vitaminphdnutrition.com. It’s really just a list of the podcasts that I’ve been on and some of the resources where I have more podcasts posted, or educational series and things like that on the gut microbiome. Then, also on the renaissanceperiodization.com. So, I have two veins for coaching. RP is for, you know, my email only coaching, and I also do video coaching through vitaminphdnutrition. Absolutely reach out. I can refer folks to good books too. So, I’m just happy to share and disseminate all the information that’s out there.
Jade: [01:03:35] You know, it’s rare – for all of you listening – I think it’s rare to have someone who’s a PhD at this level and also able to teach the way that you do. We’re incredibly grateful for you, and I will say thank you, in particular for sticking with me, educating me, and I am really happy to make a new friend and to get exposed to your work. So, thank you so much for being here.
Gabrielle: [01:04:00] You’re very welcome. Thank you for having me.