It All Starts With Your Gut: How Your Bacteria & Intestinal Inflammation Affects Your Mood, Health,

On this episode of the Ben Greenfield Fitness Podcast.

Inherently we recognize that 80% of diseases can be prevented by dealing with stress, by getting movement, getting good sleep and having good nutrition. The microcosm of what's happening in our gut is related to the macrocosm of what's happening in our world and the diversity of the microbiome. Well, that's a pretty big view.

Unproven and disproven methods and treatments. That's the official wiki definition. Would that be the same as your definition?

Health, performance, nutrition, longevity, ancestral living, biohacking and much more. My name is Ben Greenfield. Welcome to the show.

Welcome to today's show. This one is with a functional medicine doc. Talks about you, your gut, testing your gut, all sorts of other really interesting functional medicine concepts and I think you're gonna dig it. He's a smart dude. Before we jump into today's show, I want to tell you about a couple of things. First of all, we just launched our brand new Flex product at Kion. This is an all natural science backed high quality joint formula and nothing like it exists. I've been popping three at night. I bounce back honestly, almost like I'm cheating from my workouts. It knocks out joint discomfort, it knocks out soreness, it knocks out swelling. From exerc size. We've got it full of ingredients you've probably never heard of and never used before, like turmerosaccharides serrapeptase combined with proteolytic enzymes. It's super bioavailable. And there really isn't another joint product.

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Well, folks, I know a lot of you. You email me or you leave comments in a post and you say, how do I find a good doctor? What do I look for in a doctor? And it seems like nine times out of ten, I'm telling many people to at least begin by looking for a functional medicine doctor. And my guest on today's show is going to fill us in a little bit more on what exactly functional medicine is and his unique story in terms of how he now practices functional medicine. And we're also going to delve into a lot of other topics. I want to ask him about that. He's an expert in like the microbiome and some of the work he's done in terms of following Linus Pauling. And he's also a shaman. All sorts of interesting things this guy is up to. So his name is Dr. Patrick Hanaway. He's considered to be one of the world's top authorities in the realm of functional medicine. He's a board certified family physician and he's the past president of the American Board of Integrative Holistic Medicine. His practice is called Family to Family, which he runs in Asheville, beautiful area of the country. He's an initiated shaman, I believe, by a tribe in central Mexico. And he incorporates those practices in his healing approach. And he also has a long list of credentials. He was the chief medical officer at Genova Diagnostics. He was the director of medical education for the Institute for Functional Medicine. He was the medical director at the Cleveland Clinic, and just last week published a keystone article in the Journal of the American Medical association about functional medicine, which we'll dive into a little bit today. And in 2017, he won the Linus Pauling Award. So I have a feeling that Dr. Hanaway could probably speak a little bit about functional medicine. What do you think, Doc?

A little bit, yeah. I've had the great good fortune. When I was in medical school in the early 80s, I thought, well, aren't I supposed to learn about health and well being? And that wasn't what medical school was about. But I picked up a book by Dr. Jeff Bland talking about applying nutrition in clinical practice. And I'm like, okay, I'm not outside the box. Some other people are thinking about this and that was sort of the beginning of, of a long journey and feel pretty blessed in that journey over time of being able to really look at the root cause of disease and understand.

The interrelationship. I've been fascinated over time of the way in which other indigenous systems of healing have looked at it. Ayurveda, Chinese medicine, Greek, Persian medicine, Tibetan medicine, and seeing how do they interrelate, how do they see the body and the human in different ways. And I relate that to functional medicine, which is about really trying to understand why illness occurs and restoring health by addressing the root cause for each individual because we're all unique.

Does it get kind of confusing when you're merging that many different forms of.

Medicine or studying the history of all those different health practices? Because you of course have whatever constitutional typing or traditional Chinese medicine you've got Ayurvedic approaches in Eastern medicine. You have all sorts of energy based medicine in many of these shamanic practices. Do you take a little bit from each in your practice or how do you even really interpret how to navigate through that versus just sticking to one approach, like I'm an Ayurvedic doctor, for example?

Well, it's less about dabbling and it's more about synthesis and really understanding that we're really all talking about the human condition. And so within that, I like to quote Oliver Wendell Holmes Jr. Who said, I wouldn't give a fig for simplicity on this side of complexity, but I would give my right arm for simplicity on the other side of complexity. And that is beginning to see patterns of how they emerge. And so while one traditional Chinese medicine teacher said anything can come from anything, I said, well that's really fascinating, but it's not very helpful. And you know, now I see patterns. And there are patterns in each of these different views and they actually relate to each other because they follow the natural world. The patterns in the natural world are the patterns with which we move and live and the way in which life moves.

So if I were to come into your clinic and you were to assess me, for example, I would imagine you're using, since you were the former Chief Medical Officer at Genova, some form of precise quantified testing. But are you also incorporating anything else when you kind of triage a patient or you assess them when they first visit, as far as identifying which path from all these different forms of medicine is going to be best to take?

Well, the medicine that I practice is functional medicine at this point in time. And so I incorporate these other elements in as necessary as they arise. And I may use an explanation or help to understand a nuance through integrating some five element Chinese approach or thinking about Ayurveda or Tibetan Ayurveda. But my intake is really about gathering information and gathering the story, listening to the person's story. And as I'm listening to the story and the timeline of their life, what I become really interested in is when there's some emotional engagement or emotional shift in the story and I be, oh, there's something that is going to help me to understand what's under underneath. And then using that as a leverage point to be able to say, do we want to look at the mental, emotional, spiritual aspects? Do we need to look at the nutritional aspects? Do we need to look at intrinsic root causes that are going to be lifestyle, nutrition especially or something extrinsic like an antigen, an infection or a toxin that they got exposed to that kind of tipped them over in their life. And so I'm listening for all of those things so that I can retell the story in a way that they. That's like, yeah, that's what happened to me. How come no one else has ever said that? And that gives me, you know, the, the. The. The, you know, might call it the, you know, the Nerika, the opening to be able to follow the path of what's going on for that person.

So the one thing that kind of leapt out to me when I was looking at your bio was that you were initiated as a shaman. I'm curious how that happened and how that manifests itself in your. In your functional medicine practice. That's kind of a unique role for a physician.

Yeah. The Huicho people, the Veradica, who are the people who live in the Sierra Madres, Western Sierra Madres in Mexico, are one of the few people, like the Hopi in North America, who have never gone through the indoctrination of the church. And so there's still a living tradition that's been there for thousands and thousands of years. And, you know, I met some people actually in the early 90s, and I wasn't very interested in that. I was very focused on Tibetan Buddhism and Tibetan medicine and learning Ayurveda and each of those things. And I met these people and began to connect a little bit with their teachings. And then I started having a series of dreams and, you know, went to a teacher and he said, well, you need to go to this sacred place and make offerings. And so I began to follow that path and go down to Mexico and work with them two or three times a year for a week or two at a time. And I've been doing that for about 17 years now. About eight years into it, I was initiated as a marakame, is what they call their healers.

Recall that shaman is a Siberian word. And so that's what they call their healers. And we've sort of Americanized that or Anglicized that to think that everyone who's a healer within an indigenous community is a shaman. But that's actually a word that is specific to Siberian healing healers.

Really, It's a Siberian. So that's not an Amazonian term. The idea of a shaman.

Well, I mean, every indigenous culture will have their healers, will have their people who are. Who are listening to the world and listening to the spirit world as well.

So what type of practices would you incorporate in Your own, your own clinic that would be related to your training as a shaman?

Well, some of it is the way of listening. And then there are also, you know, people who come and who have, you know, I perceive an issue is a deeper, metaphysical, emotional, spiritual issue that's going on. And in that case, I'll say, you know, I really want to see you by the fire and invite them out. And we sit around the fire and I listen, and I listen in a different way. I'm really focused on.

Understanding their story at a deeper level. In those settings. I don't really focus on what your B vitamin status is or whether you had a tick bite. I'm focusing on a deeper level for that individual. And then I work with the tools that I've been given to help be able to cleanse, open, reconnect the person to their deeper sense of self.

That's really interesting. That's a fascinating background. And like I mentioned to folks, part of the reason I wanted to get you on was to kind of delve into what functional medicine actually is and how it incorporates a lot of these different methods that you've described. If you go to Wikipedia, it says functional medicine is a form of alternative medicine that encompasses a number of unproven and disproven methods and treatments. That's the official wiki definition. Would that be the same as your definition?

Well, the thing about functional medicine is that it's an operating system. It's a way of thinking and being able to work and integrate the information. So as you observed, when I was in medical school, I was interested in nutrition and I started studying acupuncture and did some mind body therapies and guided imagery. And then I learned herbology from Taroni Low Dog. And then I learned hands on healing methodology and began to do energetic healing. And I would say that when I saw patients at that period of time coming out of my training and being a family doc, and I'll note that I first spent a couple of years working in the Albuquerque Indian Hospital, working with the Pueblo people, helping to give them Western medicine, and then with the Yupik Eskimo people on the Bering Sea for a couple of years. I learned a lot of medicine, but I also learned a lot about connect, deeply connecting to people. But what I did in those times was I sort of, you know, just grabbed the latest tool that I had. I didn't have a way of integrating an operating system to put all those tools together. And that's what functional medicine does is it says, well, I'm Gonna listen to the person's story and I'm gonna try to understand, well, what are the antecedents or precursors to what was going on. Now that's gonna include looking at their genetics and looking at their family history and looking at their, their birth and what happened then. I'm gonna look for triggers like what was happening in your life at the time you started feeling ill. And by listening to the story, I can do that and I say, what are the, what are the mediators? What are the factors? You know, if we're seeing someone with an inflammatory illness, you know, are you eating inflammatory foods? And then we focus on their diet and lifestyle because inherently we recognize that 80% of diseases can be prevented, you know, by dealing with stress, by getting movement, getting good slee sleep and having good nutrition and also having meaning and purpose and connection in your life. So that's what we do with functional medicine.

Are you able to bill insurance for a lot of these kind of.

I guess as Wikipedia would define, disproven and unproven, I would say just less popular forms of medicine or at least less allopathic. But how's it work from a billing standpoint in your practice?

What we did initially was we recognized that because I'm taking more time to be with people an hour and a half back when we started. Now I take two hours and, you know, I'm gathering a bunch of information from their medical records.

Two hours. The initial meeting is two hours, initial one's two hours.

But it's also usually an hour to sometimes two hours of gathering information and reading their charts and understanding the before I even see them. And so insurance isn't going to pay for that. So we have a fee for service practice and there are some who have practices where they just get all the information in little bits of time, half an hour at a time so they can bill insurance for it. But insurance really is, it cares about it. It pays for volume, it doesn't pay for. It pays for quantity, not for quality.

Yeah. Which would be one of the underlying issues with, with a physician who is practicing an insurance based practice, really feeling as though they only get 15, 20 minutes max with a patient.

Right? Yeah. Now at Cleveland Clinic we did, we did work in an insurance model, or they still do. I'm not there anymore, but it was an hour intake and we gathered a ton of information ahead of time as well. And then would see people more closely and also have nutritionists and health coaches that were integrated, but all under an insurance billing practice. It's interesting to me, people say unproven. Well, you know, now we have an article in JAMA open from last week that says, well, when you functional medicine as a system to standard of care practice at the Cleveland Clinic that patients do better in terms of their overall outcomes.

They do better for this JAMA article and I'll link to it in the show notes. By the way, I should mention to folks, it's at BenGreenfieldFitness.com FunctionalMedicine BenGreenfieldFitness.com functionalmedicine is where I'll link to everything that Dr. Ohano and I talk about, including this latest JAMA article. But when you say they did better, are you saying they did better compared to patients who were seen by a non functional medical practitioner at the Cleveland Clinic? Correct. Interesting.

And so we set up a comparison group of people who look the same, who had the same kinds of issues and who as part of the Cleveland Clinic it's focused in being able to look at overall global outcomes measures. The tool is called PROMIS. It was a patient reported outcomes measures spent about $78 million, the NIH to put that together. And that's something that is a globally validated tool that we can say, well, when people are doing better on promis, they're doing better overall and their healthcare costs are less. So we've got another study that we're.

In the process of doing the data analysis on that's looking at cost as well because people say oh, functional medicine costs a lot of money and yet we're finding that when people are doing better they spend less money on healthcare. And so that study is not complete yet, but it's looking good.

And that other study, the one that just came out in jama, how many people did you actually look at at.

That was one where we started with over 5,000 people. We coned it down to ended up having.

Two. I don't have the numbers right in front of me, but it was like 212 people compared to 424 people, something like that. Okay, so we had a, like a two to one control. So there were two people for every one that we saw. And, and where the thing was is we needed to have people that we had data on and controls that we had data on for over a whole period of time. And that took us a little while to be able to get. So that was a limitation. But it was taking all comers wasn't taking people with a specific disease state. It's saying no matter what you show up with, we're Gonna include you in the study. And that's, you know, it's taking, it's just like clinical practice now.

I got sent this study last week and I was looking over it last week in preparation for the interview, and I thought it was more than that. I have a number of like 7,000, 7,500, something like that in my head. As far as the total number of patients enrolled in this study, is that not correct?

Well, the initial number of patients that we compared with, we started with over 1800 patients and then in functional medicine and then we had a three to one control group and so it was over 7,000. But then when you cone it down to the people who actually we have a full year's data set on and we can directly compare it ended up being. And I think my numbers are, I have to look at it again, but I think it's like 250 and 500 in the control group, something like that.

Okay, got it. Now, often on this show, we like to take that big picture overview that we just gave people on functional medicine, but also dive a little bit more into brass tacks. I know you're doing a lot, lot in your clinic when it comes to five element Chinese medicine and osteopathic manipulation and herbology. And what I'm curious about is different tools that you might use if you wanted to name a couple that you find particularly intriguing or that you find yourself using quite a bit in your practice.

Yeah, you asked that right up front. And interestingly, when I was first in practice, I probably did more testing than I needed to do to begin to understand what was going on. Now I'm at a point where I look at, I want to understand what's going on with a person nutritionally, and I can use tools that give me an opportunity to be able to look at the functional need for micronutrients of B vitamins, minerals and antioxidants. That's one kind of tool that I use that's very helpful. The other one that I've used over time is a form of stool testing to understand, well, what's going on with digestion, what's going on with inflammation, what's going on with the gut microbiome. And you know, we've just seen the explosion of information on the, on the gut microbiome. And now we see the development of new technology looking at metagenomic sequencing, such as the tool developed by onegevity Health, the gut biotest, that allows us to have, have, you know, really kind of the cutting edge understanding of what's going on. And one that is the most well validated, has the best resolution, has the best sensitivity of any kind of testing of the, of the gut microbiome.

Which one are you talking about for the microbiome? Which test?

Well, it's called, it's called Gut Bio and it's developed by Longevity Health and.

I've, I've had them on my podcast. I'll link to it in the show Notes. But I interviewed Joel Dudley and Chris Mason. Yeah, and Chris Mason. Brilliant guys. I went over there to New York to their offices and interviewed them. And shortly thereafter they started shipping these Gut Bio kits all over the states for people. I think most folks just kind of interpreted it as yet another microbiome test. But you seem to feel differently about the test and its quality.

Well, there's a couple different aspects to that. First, I'll say that, you know, as you know, I worked with Genova Diagnostics for a long period of time. I first started doing stool testing in 1991. And so I'm pretty familiar with it for some period of time. And at that point in time we just did culture and then, you know, we moved into about 10 years ago of being able to use, you know, 16s ribosomal RNA. That's just a way of being able to determine different species that are present. Each different bacteria that's in our gut has a different 16s ribosomal subunit. You don't really need to know the details of that. It's just that that's how speciation occurs. But the issue with that is that everyone had a different library. And if you had it tested through UBIome or a university or Genova diagnostics, you different results. Now, it would help us to understand shifts in community diversity. That was, all of them were helpful, but you wouldn't have a. There was no standardization that was present. And then along came the idea of doing, you know, sort of shotgun blast metagenomic sequencing, which was taking what Craig Venter did with the human biome and applying it to the gut microbiome. Now, the difference is, is that with the human, you know, biome we've got, you know, 3.6.

Million.

3.6 million base pairs. And I'm sorry, you got 3.6 million SNPs, you got about 3.6 billion base pairs, but with, and only 23,000 genes. But in the gut microbiome you have about 150 times more genetic material. And so trying to do the, the blast sequence of being able to blast everything apart and then put it all back together and say what's there? And quantify. It took a lot more.

Computing power to be able to do that. Now there are standard libraries that are done and over the past three, four years in the academic centers, this is the standard which is done is metagenomic sequencing. And I've been searching for some company that is ready to do that and bring it into clinical practice because it feels like it's a much better tool. It's where we're going.

And that's different than shotgun sequencing, right?

No, it is a shotgun sequencing.

Okay, so what you're referring to is shotgun sequencing. The other one that you think is less accurate is 16s.

Yeah, so 16s is a series of probes where we're saying, okay, we're gonna, we know that if E. Coli looks like this, we're gonna have a probe to E. Coli, but we might not have a probe to some other new bacteria that aren't there. And generally we're gonna, you know, 24 or 50 probes to be able to do that. Now when each one of us has about 150 to 250 bacteria in our gut out of a possible 2,500 that have been identified in the libraries. And we're all different and unique. So diversity in me is different than diversity in you. I like to say like, well, so diversity in Hong Kong is different than diversity in New York City is different than diversity in Paris. And we're all unique and different. But if we're just looking at a limited number of probes, we're not really going to get the whole picture of what's going on. We're going to get a limited picture. So that's one aspect of why metagenomics is important and useful. The other aspect lies with what Longevity Health has done with Chris Mason and Joel Dudley, where they're taking machine learning and artificial intelligence and being able to understand what do these patterns really mean as it relates to the symptom that people are having in their physical issues. Now we're learning from what's going on and we're beginning to describe and they've got better tools in order to be able to do that. So the gut bio test allows us to be able to say, well, we can look at the metagenomics sequence and we can understand what's happening with digestion, we can understand what's happening with inflammation, we can actually do. What you doing are called virtual metabolomics, where we can get a sense of, well, what are the short chain fatty acids that are there, which is the money in the economy of the gut. And they can begin to delve into a much deeper understanding of overall gut health. And as we know, health begins in the gut, disease begins in the gut. And so as we see changes that are going on, we're going to be able to understand relationships of what goes on in the microbiome as it relates to different stages of different diseases for different individuals, and we're going to be able to do something about it. And that's super exciting to me because it's really taking this and turning it on its ear.

Now this, I think, confuses some people and it's basically this fact that before companies like Longevity and Viome is another one that I've discussed on the show. Even though I think they use 16s.

And viome uses shotgun, I believe Viome is using transcriptomics. So it's looking at the RNA itself, not through probes, but it's looking at the RNA itself. But there's no standardization along that. Whereas with metagenomic sequencing there is. Everyone's working off of the same library around the world.

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So based on this, prior to these tests being available, I used to always recommend fol and this is right up your alley. Use something like a Genova Diagnostics GIFX stool profile, usually like a three day profile where you're getting a sampling over several days, which I understand to be a little bit more accurate than the, than the single day panel. And that is a panel that advertises itself as being able to detect, you know, most of the common parasites and then yeast and bacteria and I believe believe inflammatory markers as well, like calprotectin for example. And I think some people might be confused about whether or not getting a test like that would be redundant with getting something like a longevity gut biome test that's looking at the actual microbiome of the gut. Do people need to get both or can you get just about everything that you would get out of a GIFX panel from something like a gut box bio?

Well, that's a great question and I think the answer on that is still to be determined. So I have, you know, I worked as the medical director, chief medical officer at Genova for 10 years. You know, markers like calprotectin and pancreatic elastase were tools that I actually was the one involved in getting FDA approval and getting CBT code status for them. So I'm very familiar with them and have published on each of them. They're great individual biomarkers looking at inflammation and looking at digestion. They also. The GIFX has different ways of being able to look at the gut microbiome. It uses culture methodology that's been around for 50 plus years. It's been using the 16s probes that we talked about that are going to help us get an idea of diversity and what's going on, but they aren't going to give us all the details and they're not as sensitive. And they also have some markers of directly measuring the metabolomics, the metabolic byproducts of the bacteria. Now, what the gut biotest does is it's able to give us kind of everything that's going on there. So I can look at and say, wow, I have 198 species, here are the species and here is how much is there. And that is exactly what's in me. And I can get an understanding of what's going on virtually because they're looking at the genesis of what's happening with the bacteria in my gut. Metabolically. Those are very useful pieces of information that are not available on a test, like the GI effects.

But the individual biomarkers looking at inflammation or digestion, like calprotectin, which is a validated tool, or pancreatic elastase, which is a validated tool. Those would need to be done separately. You can get some inference on the gut biotest about an inflammation score based upon the machine learning that Joel Dudley has helped put together. You can get an understanding of what's happening with digestion based upon who's living in the hood that are helpful with digestion, but you don't get an exact answer.

Interesting. So at this point, if you wanted the, the best of both worlds, you'd have to get both tests. It sounds like that would be appropriate if you wanted to see everything that was going on in the gut. You'd have to get like a GIFX panel and a gut bio panel, or.

You can get some of the individual biomarkers like pancreatic elastase and calprotectin from just about any laboratory in the country and then look at the gut bio test to really get an understanding of the gut microbiome. There's, there's no better test for the gut microbiome than what longevity health has put together.

Oh, that's a, that's A powerful statement. Okay.

The, the, the GI effects panel, then like you mentioned, you probably could save some money by just getting like calprotectin and pancreatic elastase and a few of the things you wouldn't be getting with something like a gut bio. Do you think that in the future some of these microbiome tests like the gut bio, would also be able to offer those type of markers on the panel?

I'm hoping we can get there.

Yeah, that would be cool. To only have to fiddle around with one.

Yeah. And part of it, Ben, is they're going to be working on doing the comparisons to see can you actually predict exactly what the calprotectin level is going to be. That's what the beauty of what Joel Dudley's work is and the machine learning is to be able to make those comparisons. We don't know that yet. For example, there is a low level inflammation that we have. A pretty good idea is happening for a lot of people that's based in the microbiome. And we don't see changes in inflammatory markers of the gut yet and we don't see changes in crp. But we know that there's something that's going on with inflammation. We look at these millions of people with autoimmune diseases and we're not actually able to pick up where's the inflammation. We know there's something going on with the immune system system, and it's our hope that we're going to be able to characterize that with the gut biotest and metagenomic sequencing and machine learning and virtual metabolomics. So that's to me, where the puck is going.

Okay, got it. And again, kind of boots on the ground. Can you give me an example of something that you might see or perhaps even as you just alluded to with the case of inflammation, something you see repeatedly on something like a gut biological bio in many people. And what steps, from a functional medicine standpoint you would then take to address something like that?

Well, with the gut biotest, where I'm going is I'm looking at some of the scores that are put together, where we're going to look at a microbiome based inflammation score. And that's going to tell me, okay, so here's an inflammation that's going on. Now I need to work with some specific agents and they may be fish oils and omega 3 fats. They may be using turmeric and various formulations of turmeric at therapeutic doses, 500 to 1,000 milligrams, twice a day they may be using Boswellia. I've got a whole series of kinds of things and tools that I work with that I'm able to apply. When I know that there is an inflammatory issue that's going on, or if I see that there's a permeability issue that's going on, then that I can tell from the gut bio test. So with each of these factors, I'm getting deeper into an understanding. Now where they're going is being able to take that not only look at the immune system, but to more deeply look at digestion, to understand where your fiber needs are, but also being able to look at the enteric nervous system and the whole brain gut microbiome connection, which is fascinating. We see this whole idea of psychobiology and prebiotics that are going to help the bacteria that will have an effect on your mood, on depression and anxiety. And this to me is really a whole fascinating new field that we're going to be looking at the gut to treat patients who have, you know, depression and anxiety and mental health and neurological disorders. That's really fascinating.

That's interesting. And not many people have used the term psychobiotics on the show before, but I, I know it's been several years now since articles have been appearing on PubMed about this idea that probiotics, when ingested, can confer beneficial effects to the central nervous system and regulate the HPA axis and the glucocorticoid stress response. It's very interesting that these things in a way are almost like mini psychedelics.

Well, you can think of them that way or you can think of them. I'm actually more interested in what, what are the foods and what are the prebiotics that help your bacteria to grow, to be able to bring balance back to the system overall. And so here's. Let me give you an example of how sort of the, if you will, the oddness of my thinking, but how these pieces fit together is that we know that through.

The gut it produces cytokines that may be pro or anti inflammatory. It produces metabolites. There are more metabolites that come from our gut than there are circulating from our own cells. There's information that is stimulated from the vagal nerve going back up to the brain. There are neurotransmitters like serotonin. 95% of the serotonin in the body is in the gut. All that information is going up into the brain. Ten times more information going in that direction than in the other direction. Now where it goes is it goes first, to the amygdala, which is involved in our emotional relationship to the world. World and gathers information from our memory. And it goes to another place called the insular cortex. And our insular cortex is a small little area that helps to define our own sense of self. So from there, that information then goes to the HPA axis and determines what's going to happen hormonally. It goes to our whole reactivity. It connects to our emotions. So to me, like, okay, so what I'm taking in from the environment, the dog that I'm touching, the water that I'm drinking or bathing in, the food that I'm eating, every environmental input is being related to or filtered through my gut microbiome. And it's sending signals to my brain that help me to understand who I am and how do I relate to the world and what is the emotional connection. Well, that to me is super fascinating because it now puts us in direct relationship where the microcosm of what's happening in our gut is related to the macrocosm of what's happening in our world and the diversity of the microbiome. And it connects to our own sense of self and relationship to the world. Well, that's a pretty big view. And that's a view that systems like Ayurveda and traditional Chinese medicine have talked about for a long time of how those elements fit together. That's what I'm interested in.

That's really fascinating. And for those of you interested, I'll link to a paper on this concept of psychobiotics in the shownotes@bengreenfieldfitness.com FunctionalMedicine if you want to dig into this a little bit more, it's a fascinating field. You said that earlier, Dr. Hanaway. All health begins in the gut. Or you, you start with the gut or something to that effect. But wouldn't there be some exceptions to that? For example, like a traumatic brain injury or a concussion?

That might be a situation where it kind of starts with the head, right? Because we know that bacterial infections in the GI tract seem to pop up in response to brain inflammation. And there tends to be kind of a shift in gut health. And often gut dysfunction frequently follows a traumatic brain injury. Injury. Do you ever kind of start higher up? Start with the, the computer up in the skull?

Hardly ever. Because, you know, we are now learning that and we, we've known for some time that there's a relationship between the intestinal permeability in the gut and the blood brain permeability. Now, what we've learned more recently is that when people have concussions and traumatic brain injury, it actually changes intestinal permeability. So now why do you have more increased risk of infections? Well, you've got more permeability that's going on. So when I'm treating someone who's got a traumatic brain injury or concussion, I'm going to use anti inflammatories and fish oils, you know, at high doses to be able to help them out. But I'm also going to be focusing on how do I ensure that the, the intestinal permeability is taken care of, that there's no leakiness in the gut gut. And so I'm going to be using agents like, you know, glutamine and aloe and large arabinol, galactans and other kinds of things that are going to be helping to heal the lining of the gut as well, where most people aren't necessarily thinking that way.

Okay, so, so you can work on the blood brain barrier and the gut blood barrier simultaneously in a situation like that.

The, the gut barrier, absolutely. And it's necessary to be able to do so. So it's odd to, you know, you recognize, wow, concussions lead to changes in intestinal permeability. Who would have guessed that? And yet, you know, these things are intimately related to each other. So I do, you know, look at what's going on with the microbiome so that I can have the right bacteria that the right gut microbiome that's there so that it's helping to soothe that. There is more, you know, GABA being released and there's some great papers, as you said, that study. And look at what are the specific probiotics that are going to help to cause some down regulation of brain activity and down regulation of brain inflammation that's going on. And for myself, Ben, I continue to look to, well, what are the prebiotics and what are the foods that can actually do that? I'm more interested in that than I am in trying to find the designer probiotics. Probiotics are useful therapeutically. But recall that they're tourists. They come in and they affect the economy of what's going on in the gut while they're there. And then they leave. They're gone. They're gone within 13 days after ingesting them. So they may have some long lasting effect like a, like a tourist economy does in the town of Asheville, where I live. But you don't want to be reliant on that. You want to be able to provide the foods that are going to help the good bacteria in your own gut to be able to grow. And we know that diet changes the microbiome within one to two days, but you got to stay on that new diet.

Yeah, yeah. Speaking of tbi, I know they're also now looking into things like fecal microbiota. Transplant is one method of addressing a lot of the inflammation. Have you looked into that in your clinic at all yet, or is that something you have your eyes on?

Well, I have. I have for some time, actually. I went and met with Tom Berati in Sydney, Australia, about 11 years ago to learn how this was done and came back with the idea that I wanted to start to do this in practice and talked with a colleague about it. And then I had an interesting experience. I met with one of the foremost GI researchers, Fergus Shanahan in Cork, who focuses on inflammatory bowel disease. And he's been working with these kinds of tools. And he said to me, patrick, if the microbiome can have an effect on causing cancer and heart disease and autoimmune disease and. And inflammatory bowel disease and just about anything, if you're giving someone else someone else's microbiome.

Do you really understand what risk you're giving at that point in time? You can make sure that it doesn't have any infection in it, but are you potentially giving them some other disease that they wouldn't have had because you're transplanting their microbiome in there? And that gave me pause, and I said, well, you know, we really don't know enough. And that is why the FDA has. Has labeled it as, you know, the fecal microbial transplant as a drug and has limited studies on it. And there's some fascinating new research that's coming out and some new companies that are coming out looking at. At the poop pill and the ability to be able to do that. And in fact, just yesterday, or I guess it was on the 30th in the New England Journal, there were a series of articles that came. Came out talking about two patients who died from fecal microbial transplant and how we actually screen stool for being able to do that and how to set standards that have not been there for fecal microbial transplant. So I find it to be an important and powerful tool and not something that I want to just have my patients do, you know, have a DIY mechanism, mechanism for doing it by buying a blender at Goodwill, you know, and getting their best friend's poop and doing a transplant. I don't think that's a good idea.

Yeah. And I actually saw that, that report about the couple of folks who died from the fmt, and that was even with a pill that wasn't like they were hanging themselves upside down their living room and, you know, dumping a bunch of poop up their backsides. They were actually just using like encapsulated stool transplantation.

Right. And there's a couple of companies that are doing that, but they're, you know, and there's also some that are going through, you know, phase two and phase three clinical trials, trials to be able to look at not only recurrent C. Diff, which is where it has been validated, and these patients, you know, can die from that. And it's got a 90% cure rate. So that's a good idea. But if you've got someone with irritable bowel syndrome, you know, do you really want to do that? Take on some unknown risk? It looks like it's going to be helpful for ulcerative colitis. There's some fascinating studies around and its role in autism spectrum disorder and those are in phase two trials at this point in time. And there are some other things that raise a question that there's a subset of patients who have type 2 diabetes and pre diabetes and metabolic syndrome who may benefit from it, but we don't know yet. Well, what do we need to give them and which subset of patients are actually going to respond and we don't know the other risks, so. So I'm gonna let the process bear itself out rather than have patients do it themselves.

Yeah, yeah. And by the way, I think it was E. Coli that those folks wound up being infected with like an antibiotic resistant form of E. Coli. Which is sad.

Exactly.

Now, you talked about how you actually don't really like to go to designer based probiotics and you instead like to use food as much as possible to modulate the biome. I'm curious if there are particular foods that you find yourself repeatedly turning to in your practice, whether it's a. Like I interviewed Dr. William Davis and he has a L. Routiri strain of yogurt that he's very keen on and recommends to a lot of his patients for that gut brain connection, increasing oxytocin and decreasing appetite cravings. And also he's seen some positive responses in body content composition and things like that with that strain which he actually describes. If folks are listening, they go listen to my podcast with Dr. Davis. But how about you? Do you have any special yogurt recipes or kimchi or sauerkraut or anything. You're really recommending a lot to people.

Well, it's focusing on being able to work with fermented foods and finding out culturally where they're at. Are you going to eat kimchi? Some people will. Some people hate it. Are you going to eat sauerkraut? Some people will. Some people. People won't. You know, working with yogurts that they make themselves. I particularly work with goat yogurts and I'm a big fan of some of the coconut kefirs that are out there because so those are all foods that are going to, you know, have. They're going to be fermented and they're going to have live bacteria that are present in them. More at this point in time, I'm going to saying, well, what can we do with acacia root?

And you, what can.

Can we use with.

Bioflavonoids and isoflavones from pomegranate, from blueberry, from cranberry, all of which help to activate the beneficial bacteria to be able to grow. And so previously we'd use fructooligosaccharides in inulin, but no, now I'm focusing more on modified citrus pectin, acacia root and these other agents as simple, specific ways of helping the beneficial bacteria, bacteria to be able to grow in the gut. I use probiotics when I'm using them therapeutically. So if I've got a patient, you know, who's got inflammatory bowel disease, you know, I'm using a combination of, you know, four strains of four species of bifido and three species of lacto and strepthermophilus at specific doses, you know, to induce remission. I know it works. The data is pretty clear. If I've got someone with ibs, there's a couple different probiotic formulations that I'm going to use. Use Bifidobacter infantis 35624, clearly demonstrated in the literature. There's some other combinations of lacto and bifido that have also worked well. We're learning new things every day. In terms of that I'm less focused on. Here's the probiotic that's good for everything because the probiotics that are good for dealing with monilio vaginitis and recurrent can problems are different. When I'm working with someone who is getting an antibiotic for some reason, even if I may need it to use it to help clean out their gut, that's really got a pathogenic Dysbiosis that's going on. I'm going to use Saccharomyces boulardii along with that. If I've got someone who I think has problems with biofilm, I'm going to use a product called Biofilm Biome Health. That's a wonderful combination product to be able to do. But again they're all for specific therapeutic indications.

Yeah. And. Well, how about pomegranate peel extract? That's something that I've come across quite a bit now kind of being used as a sort of prebiotic. And particularly what intrigued me, I came across this when I was working on some research for this new book or chapter in this new book I'm really releasing on anti aging and longevity. How this pomegranate peel extract is actually helping to produce something called urolithin A in the gut. Urolithin A is something that seems to, especially in aging humans, support, you know, mitochondrial health and mitophagy and mitochondrial biogenesis. And having this pomegranate peel is part of a fermented food rich diet or probiotic protocol appears to be a really good way to do that. Have you started to use any form of pomegranate in your practice at all?

Well, I have through products that look at pomegranate extract to be able to help with the gut bacteria, to help as a prebiotic and an isoflavone that really helps to improve and shift the overall diversity in the microbiome including increase increasing akkermansia which is anti inflammatory in nature. But I've also found that other forms of ellagic acid which is the active ingredient in pomegranate, I'm not sure if it's in pomegranate peel. I'm not sure about that aspect of it. But other pomegranate extracts are focusing on ellagic acid and how to be able to use that as a measure to modify the urolithins that are present there. But I'm not familiar with the anti aging research that you're talking about and I'd love to learn more about that.

Yeah, it's called urolithin A. I'll try and hunt down one of the, One of the PubMed studies on this and put a link to it in the show notes for folks. And I think it's both the seed and the peel, but I believe the peel is where the majority of those compounds reside. So that's an interesting fruit. And the more I see on pomegranate, the more, more I think that that's probably if you're going to choose one fruit to consume regularly, that'd probably be one of them.

Yeah. I also am familiar with some fascinating research on the pomegranate extract and ellagic acid that is specific to decreasing diabetes and prediabetes and metabolic syndrome.

Yeah, yeah, it's interesting. Now a couple other things that I wanted to talk to you about about and that is we discussed longevity and this gut bio testing and how that's one of your go to's as far as like kind of a staple of your functional medicine practice, starting with the gut, but when it comes to other tests that you might find yourself running frequently. Again I have to ask you this. Just knowing your background in Genova diagnostics, whether it's a micronutrient analysis or urine urinary panel, are there other kind of go to tests that you find to be particularly informative?

Well, I mentioned right up front looking at nutritional status of an individual. So there's a test there called the Nutrival that is a combination of urinary organic acids, plasma amino acids, whole blood fatty acids, markers of oxidative stress and then whole blood molecular markers of minerals, both nutritive and toxic minerals, heavy metals that is synthesized together in an algorithm that helps to give very specific recommendations around antioxidants, B vitamins and minerals and what can be done. It gives some additional information beyond that about.

Mitochondrial function, about toxic exposure, about methylation. And that's a tool that, that myself and my team helped put together about 13 years ago. That is an algorithm that's based upon the peer reviewed literature and is well thought through and I use that a lot in my practice.

Yeah, you're probably like the 10th doctor that's recommended that on the show. That Nutrival test, I mean it's extremely comprehensive and with that one, even the information that comes with it, like the sample request report and you know, folks are to go to like the Genova diagnostics website, you could, you could see a sample report. I mean it's, it's honestly something that even a patient can go through and read and get a lot of good information from. You know, I find it to be a pretty user friendly test.

Well, I appreciate that because it was, you know, our team was deeply involved in the design of that because that's what we wanted it to be, is helping patients to understand how to improve their own health and well being.

Yeah.

And that, that test now from what I understand they're also doing the option to add genomics onto that. Like look at like your MTHFR SNPs or your COMT or APOE or things like that. Right?

That's exactly right. So that is a value add that you can do. Patients I do also like to, you know, if patients have 23andMe data, many, many people do and take that and run that through and algorithm like, you know, Rhonda Patrick's found my fitness or the pure genomics algorithm or Intellect's DNA. There's a number of aftermarket tools and I just sort of say it's important if you're going to use those to use tools that are well curated and well validated, not tools that are just trying to sell a product, you know, in the aftermarket use of gas, gathering information from your 23andMe data. So I'll do that with some patients. You asked about other testing. I'll just say that I'm looking at extrinsic factors of triggers. So I may do heavy metal testing where I'm looking at a provocation test to measure a toxic element clearance and see do they have excess heavy metals. I may do tick borne illness testing that's going on. I like to work with isolation because I find that I don't have to deal with the false negative tests that I may get from the standard laboratories. You know, those are some of the common things that I use. Hormonal testing, sometimes urinary hormonal testing, sometimes I'll work with Genova Diagnostics, sometimes I'll work with Precision Analytic and their Dutch test which is both of them.

They're pretty much the same test and they're both, both great tools for helping me to understand.

Yeah, the genetic tool I used to use for a while just because it was very simple and clean and cost like 10 bucks I believe to upload your 23andMe data to was Promethease and they were since acquired by MyHeritage and I've been keeping my eye on MyHeritage. It looks like they're kind of running out some cool tests that delve into a little bit more than, than you'd get from your 23andMe data. And then of course for folks who want to do it all, you can do the whole genome sequencing which I think it's a company in LA now, Health Nucleus is now offering that. But yeah, I get a lot of interesting data out of the genetics as well.

Yeah, so Health Nucleus, yeah, I mean they're out of San Diego. That's.

The company that was first started by Craig Benter there. But the issue is that you can't take that data and put it through some of the, some of the aftermarket tools yet. They're not set to be able to get the whole genome data. And I particularly like Rhonda Patrick's Found My Fitness. I found that she's got really good curation of the data, continues to update it, and is taking the 23andMe data. That's one I like to use with patients.

Yeah, yeah. And hers is. Is it just called Found My Fitness?

Yeah.

Okay, cool, cool. I'll link to that in the show. Notes for folks. Now, one other thing that I wanted to ask you regarding functional medicine was I know, kind of similar to how a guy like me is getting around to different health conferences and fitness conferences and keeping my finger on the pulse of what the latest energy drink or ab training device is. I know you get around to a lot of functional medicine conferences and I'm curious if, coming down the pipeline, there are any particularly intriguing or hot topics these days that are being talked about at these functional medicine conferences.

The big questions have been in relationship to dealing with autoimmune disease and dealing with cognitive impairment. There's so many people who are interested and concerned about, well, what can I do to ensure that my memory is not going to deteriorate and how do I evaluate that and what kinds of supplements and support can I use use? Dale Bredesen's work has kind of opened the door on all that. I find it to be really useful consideration. And we have seen that there's certainly a subset of patients, not everybody, but a significant subset of patients who do have a reversal of their cognitive impairment from taking these approaches that are going to include, you know, diet and lifestyle, exercise and being able to define, well, where's the problem? Where's the imbalance that's going on? Is it related to an APOE 4 status where I need to really pay attention to toxin exposure and antioxidants and look for infections, or is it related to some hormonal imbalances where I'm more atrophic, or is it related to a metabolic syndrome kind of a glucose toxicity issue? And I like the way in which Dale has framed that out. And those are big issues in the current state, as well as autoimmune disease, because we see so many people with non specific autoimmune diseases and they really are under the big category of 100 plus diseases that is affecting 54 million Americans at this point in time. And from a functional medicine perspective, we're thinking about them in A similar way, we're not trying to stratify into what do I do for.

Ankylosing spondylitis or what do I do for Sjogren's disease. Rather we're looking at, well, what do I do for autoimmune disease? And then there may be some specific things that for ankylosing spondylitis, 1, I'll just pick that. You know, it's like we see these biologic drugs being advertised at night on TV to individuals and yet it's related to a genetic predisposition with intestinal permeability in the presence of a specific eclipsiella that is a reactive to, into the, in the joints, in the lower back that induces that. So, gosh, we want to deal with permeability in the gut microbiome when we're dealing with that. And here we are back to the same thing that we've been talking about. So those are some big things that are out there from the disease standpoint and then from the, from the standpoint of how do we look at the individual. I think, you know, we've already been talking about the importance of the microbiome and how to understand it. And I think one of the things that I try to emphasize is that it's really about the community that's present of the microbiome. It's not so much about the individual microbes that are present in your gut. Now in certain pathogenic cases, that's true, but generally I'm not trying to increase someone's Akkermansia. I'm not trying to decrease someone's methanobacter. I'm trying to help the overall population to move into balance. And this is something that a systems approach and a machine learning approach like Gut Bio is using is something that is taking that into account and it's not trying to just focus on, oh, I see a lack of Bifidobacter. So I'm going to dump a lot of Bifidobacter in the system. That's sort of how we used to do it twice 20 years ago. And we would force changes in the system by giving a big input, but it's not a long term therapeutic option.

Yeah, interesting. Well, I mean, I think one big takeaway here for folks, at least for me personally, would be a quantify the biome use something like Gut Bio to actually see what's going on. Baby use. Rather than putting all of your efforts towards some targeted probiotic regime instead, wide variety of fermented foods and both prebiotics and probiotics from a food based standpoint. And then finally address the actual gut lining. I know there are a ton of nutrients that can assist with that, from bone broth to colostrum to L glutamine. And I think that your approach of starting with the gut seems like a very, very sound place to begin.

Exactly. And all those. And thanks for talking about colostrum and bone broth. The bone broths are so important and so nutritive. I found in my own healing process, having the bone broths on an everyday basis was something that was very, very nourishing to me.

Yeah. That's a daily staple in my own diet. Now when I'm home is a big. I use the kettle and fire bone broth and do a big carton of that. And then I get these vegetable powders from this guy, Dr. Thomas Cowan, his powdered heirloom vegetables. And I'll put a bunch of those into the bone broth. And that's just like my tonic at lunch every day. And you almost feel it going to work in your gut right after you drink it.

Yeah. And Thomas has written some really fascinating things in terms of health and well being and connecting back to the earth. It's really not a dissimilar view from what I'm talking about.

Yeah. All you guys are doing a great job. And Tom's been on the show a few times before. As an Asheville citizen, I would be remiss not to ask you about whether or not you've actually been to this, this place that blew my mind the last time I was there. It's a. It's a massive food city with wonderful restaurants. But before I headed to the airport, I think it was on a Saturday morning, I went and stood in line at this place called Biscuit Head for what people told me were, you need to do this before you die. And I was prepared for heart attack on a plate. Right. I kind of prepared for mentally. And then I got there and they have like gluten free vegan biscuits and sweet potato coconut milk gravy and actually a pretty decent menu if you wanted to go at your biscuits and gravy from a health standpoint. But it was probably one of the better breakfasts I've had in the past three years or so. It was last year I visited this place, Biscuit Head. Have you been?

Oh yeah, many times. And biscuits with the pictures of cats all over and then the saying that says biscuits as big as a cat's head. Yeah, I've been there Many times. And they've got lots of different kinds of bacon. They've got the bacon of the day. That's a great add on with that. Yeah, I love to go there.

Oh yeah, Grits and fried catfish and fried green tomatoes.

That works.

So if any of you listen to.

It and you a couple times a.

Year, if you happen to be swinging through Asheville, swing by that biscuit head place. Well, I've been taking some notes as we've been chatting and if any listeners want to go to BenGreenfieldFitness.com FunctionalMedicine I'll link to Dr. Hanaway's practice there, family to family in Asheville. And then I will also link to everything from that recent JAMA article that came out showing the benefits of functional medicine, as well as several of the studies that I mentioned about everything from pomegranate peel extract to psychobio biotics. I'll link to the previous episode that I did with the two scientists from Longevity, Joel Dudley and Chris Mason. On a little bit more detail. We geeked out for like 90 minutes on how that test works. So if you're still kind of a little bit confused about say, shotgun sequencing versus 16s, that would be a good episode for you to listen to. And I'll also link to some of these tests that we talked about like Nutraval and, and the Dutch test and the found my fitness genetic tools and, and of course, course I'll even, I'll even hunt down a link to Biscuit Head for you guys and put that in there as well so you can go download those menus and, and, and salivate in the meantime. Dr. Hanaway, thanks for coming on the show and sharing all this stuff with us, man.

You bet. Thanks so much, Ben.

All right, folks, I'm Ben Greenfield and Dr. Patrick Hanaway signing out from BenGreenfieldFitness.com have an amazing week.

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