- Chris Kresser - http://chriskresser.com -
Episode 9 – the “gut-brain axis”
Posted By Chris Kresser On May 10, 2011 @ 9:33 am In Podcasts | 36 Comments
In this episode we discuss the gut-brain axis: the relationship between digestive health and cognitive function, memory, depression, anxiety and other mental and behavioral health issues. We cover:
I think the gut-brain axis is one of the most important and least recognized factors in human health. If you follow a good diet (Paleo, Primal, Perfect Health Diet, etc.) and you’re still experiencing gut symptoms, it’s likely you have a gut-brain axis issue.
DANNY RODDY: Hello everyone and welcome to the Healthy Skeptic podcast. My name is Danny Roddy and with me is Chris Kresser, health detective and creator of thehealthyskeptic.org, a blog challenging mainstream myths about nutrition and health. Chris, how are you doin buddy?
CHRIS KRESSER: I’m pretty good Danny, how bout you?
DANNY RODDY: I’m doing really great, but when I walked into my garage, my podcasting studio, I forgot to plug in my deep freezer from two weeks ago, so there was spoiled beef fat that smelled absolutely terrible.
CHRIS KRESSER: You’re bringing this whole garage band thing to a new level huh.
DANNY RODDY: Cleaning out the deep freezer was one of the worst moments of my life, also because it was a ton of expensive spoiled meat.
CHRIS KRESSER: Yeah that’s what I was gonna say.
DANNY RODDY: But the smell, oh my God.
CHRIS KRESSER: That would be catastrophic for us, we buy like, a quarter of a cow at a time, it’s like $500-600 bucks of meat, if that happened I would be really really upset.
DANNY RODDY: Every single time we podcast I tell myself, you need to like make a note because you’re totally gonna forget and I forgot.
CHRIS KRESSER: Maybe we need the Danny Roddy grass-fed beef fund.
DANNY RODDY: It’s okay I’ll get by. It was mostly fat, which I’m more happy about, cause I think it’s like, way less expensive.
CHRIS KRESSER: Yeah, definitely. Good.
DANNY RODDY: What’s new with you?
CHRIS KRESSER: Um, ya know just slowly getting settled in to our new place, and when I say slowly I mean it. My office probably still has probably 14 unpacked boxes that I’m surrounded by. I’ve just been too busy to unpack em and it’s gonna stay like that for the next couple weeks until we get the healthy baby product out, which, I’ll talk a little bit about at the end, cause it’s coming up. I’m pretty excited about that. Yeah otherwise I’m happy to see the spring here it’s a beautiful, sunny, windy, crisp day in the bay area, I like that kinda day, so I’m good.
DANNY RODDY: That’s exactly how it is down here too. Awesome so this week’s episode is gonna specialize in the gut-brain axis. Do you wanna tell us a little more about it?
CHRIS KRESSER: The gut-brain axis, the axis of evil. Sounds kind of sci-fi, but actually it’s probably one of the most important and most often ignored aspects of health and I think the more I see patients and the more I get into this research, the more important I’m seeing it and the more significant I think it is, especially in people who are doing all the right things in terms of gut health and they’re not improving. And that’s actually a significant percentage of the patients I see, fall into that category, so it’s one of the reasons I’ve been pursuing this as an avenue of research.
DANNY RODDY: It seems like it’s kind of a black box mysterious thing to treat, I hear everybody talking about but it seems very up in the air, is it just because it’s so new, do you think?
CHRIS KRESSER: Um, I think that’s partly it but I actually think that it’s related to what we’ve been talking about a lot that some of the treatments for it are, involve lifestyle changes that are a lot more difficult to make than just switching up your supplement regime or the percentage of carbohydrates you eat every day. I know people are probably getting tired of hearing me say this but, the whole stress management piece is so crucial and yet I think it’s the hardest thing we can do in terms of making changes in our health. We’ll talk about that at the end when we talk about how to work with gut-brain axis issues.
I’ll talk a little bit generally about what I mean when I say the gut-brain axis cause it’s complex but it’s also completely simple. It’s probably obvious but I’ll say it anyways, everything we’ve ever done in life, or everything we ever will do depends on the brain. Anything from our capacity to taste food or appreciate art or music or smell, to feel the sun or the wind on our skin. To enjoy activities, to read, to record a podcast, it depends on our brain. And if the brain’s not functioning well, nothing else in the body will function well, period. And that’s so important to get. It’s one of those really obvious things that’s so obvious maybe that we overlook it.
DANNY RODDY: Is it the chicken or the egg syndrome though, because I feel like foods I eat specifically make me happy or sad, or is that a mental thing? Do you know which comes first?
CHRIS KRESSER: I think the sooner we get rid of this idea of linear causality in the body the better. One of the coolest things about Chinese medicine (and Chinese philosophy in general) is that they don’t really tend to see things in linear fashion. They see things in a cyclical way. And they way they look at the body, they would never say ‘this causes that’, like from A to B. It’s always ‘this and that’. Or, ‘and both’. For example, they’ve always recognized that the emotions, psychology, and physiology are one in the same. In fact they don’t even really have a separate word for emotions, like in the medical sense. Of course they do in language, but they look at systems of the body. The liver system, or the lung system, or the heart system. Each system includes both physical symptoms and also emotional and psychological and even psycho-spiritual aspects. So it’s a pretty cool way of looking at the body and I think in that sense it’s more advanced than our way of looking at it, which is ya know, like a car, with a bunch of separate parts. We understand that they’re related but we still talk about them as being and distinct. But the truth is, you can’t really talk about emotion without talking about physiology. And you can’t talk about physiology without talking about emotion. They’re not connected, they’re the same system. So I think that’s important to understand and it kinda makes the chicken and egg thing a moot point. In the sense that it’s really difficult, if it’s all part of the same system it’s really difficult to say which came first and which followed. Once you’re in the cycle you’re in the cycle. So, that’s good news, bad news because it means that when it comes to treating it, you don’t have to figure out which one. You do both and both will improve. But you can figure out which one you havn’t been focusing on, which in most cases for most people is the brain. And so you might get more milage by focusing on one area because you’ve been neglecting it.
DANNY RODDY: I like that cyclical thing, I’ve never heard that before.
CHRIS KRESSER: Yeah Chinese medicine, they’re amazingly far, far ahead of they’re time. They figured this stuff out 2500, 3000 years ago. While we were still thinking about things in terms of phlegm and bile, western medicine was just a totally archaic understanding the body.
DANNY RODDY: Phrenology?
CHRIS KRESSER: Yeah, you were a phlegm type, or a bile type, and you know even up until the middle ages we were bleeding buckets full of blood from people to make them better. Ya know George Washington was killed by his physician who just kept bleeding him and bleeding him. He was sick but he just kept bleeding him til he died. Anyways I don’t know where the heck we’re going with this, but lemme get back on track here.. the brain.
When the brain’s not functioning well nothing else in the body functions well. So you have to also remember that neurons are post-mitotic which means they don’t go through cell division, they don’t regenerate. They’re like heart tissue in that respect which is the only other post-mitotic tissue in the body. So when neurons die that’s it. You don’t get new ones, game over. So for example by the time you finish listening to this podcast you’ll probably have lost about 7,000 neurons. Sorry to say, it depends what you’re doing while you’re listening too but, and the day that we’re born we have more neurons than we’ll ever have in our life. So that’s the bad news but the good news is that the neurons can develop plasticity, which means that when you lose neurons, other neurons can adapt to communicate with each other so you can form these new connections that can take the place in some cases of the loss of neurons.
What all this means is that protecting the brain from neuro-degeneration, which is happening for all of us all the time, and when I say protecting I don’t mean stopping cause you can’t, at least we don’t know how to yet. I mean slowing it down as much as possible. This is one of the most important and again overlooked steps we can take in protecting our health.
So let’s talk a little bit more specifically about the brain-gut axis and how it all works. The 50,000 foot overview, which somebody on the facebook page asked for, is this… 90% of our brain’s output goes into something called the pontomedullary area, it’s the lower two-thirds of the brain stem, and that goes into the vagus, or the pneumogastric nerve, which innervates the digestive tract. Now one of the earliest signs of the brain not firing well is poor vagal activity, which will manifest as decreased pancreatic enzyme secretion, poor gallbladder function, and poor gut function overall. And it basically works like this, you have decreased activity in the brain, and we’re gonna talk about how that can happen in a second, and that decreases the activation of the vagal motor nuclei, which in turns suppresses the intestinal immune system and decreases intestinal blood flow. And when that happens you get an increased growth in pathogenic yeast and bacteria, that cause intestinal permeability or leaky gut, which we’ve talked about a lot, and leaky gut causes a state of chronic low grade inflammation. Then the inflammatory cytokines produced in the gut travel through the blood and they cross the blood-brain barrier. One of the problems with inflammation is that it makes the blood-brain barrier leaky so you get leaky brain. And then those inflammatory cytokines once they get into the brain activate the microglial cells, which are the second type of cell in the brain. You have neurons and then you have microglial cells. The microglial cells are the immune cells of the brain and once they’re activated by these inflammatory cytokines this is basically inflammation of the brain. So your brain gets inflamed, you get a leaky brain and then you get inflamed brain. And that’s no fun, definitely. Cause one of the problems is that unlike the rest of the immune system in the body that has T-regulatory cells that can turn off inflammation in the brain, the microglial cells don’t get turned off. So, when you’ve got an inflamed brain it can be really tricky to reduce that inflammation without some outside help. So, you’ve got an inflamed brain and the inflammation in the brain decreases nerve conductance and that in turn causes depression and reduced activity of the vagal motor nuclei, and of course then we’re back where we started. That reduced activity of the brain reduces the output into the vagus, and that causes more digestive problems, more inflammation in the gut, more inflammatory cytokines to be in the bloodstream and up into the brain and we’re stuck in this really viscous cycle.
DANNY RODDY: Cyclical
CHRIS KRESSER: Cyclical, exactly, more cycles, it’s all cycles baby! So, this is also why digestive symptoms are typically the main symptom of brain issues. I don’t know if you’ve ever thought about this, but two of the populations that most commonly have gut symptoms are seniors and autistic kids. I mean, show me an autistic kid and I’ll show you someone that’s got a screwed up gut. As Datis Kharazzian likes to say. And seniors typically have problems chewing, they have hypochloridia or atrophic gastritis where they don’t produce stomach acid, they’re constipated. It’s very very common to see digestive problems in seniors and it’s not a coincidence, it’s not, there’s a mechanism here and that mechanism is neurodegeneration and neuroinflammation. The other thing that’s important to recognize about all this, which we already alluded to, is that when gut symptoms persist even in the context of a healthy diet, like let’s say you’ve done the 30-day challenge or your on a paleo diet and you’re still having a lot of symptoms, that could indicate a brain-gut axis problem. It may also indicate a parasite or something like that, but let’s say you’ve been tested for a parasite and you don’t have any but you’re still having all these gut symptoms, that’s the brain-gut axis or the gut-brain axis right there.
DANNY RODDY: Could heavy metals be another factor?
CHRIS KRESSER: Sure, I mean any kind of environmental toxin, including metals, could be a factor in terms of agitating the gut and causing inflammation. And also, I think as you’re suggesting, causing issues in the brain. But, the body is equipped to deal with some level of metal toxicity and of course there certainly are people who have more exposure to toxic metals than they can handle, but I think heavy metal toxicity is also one of these diagnoses that fall into that sort of like, candida, chronic fatigue, lime disease category.
DANNY RODDY: I couldn’t agree more, just because the amount of people with amalgams in their mouth and that are unaffected by them is huge so it’s like some people it affects really badly and then other people it’s like totally okay.
CHRIS KRESSER: Right so my mantra lately is ‘it’s the environment stupid’. Which is like, we’re always trying to find the answer for everybody, but the truth is, and I was just talking to a patient about this yesterday, there is no answer for everybody because everyone’s internal environment is different. So for example, you take one person and they have Blastocystis hominis, which is the most common parasite in humans and they have no symptoms, they’re completely healthy, completely symptom free. Take another person and they have blasto and they’re totally sick. They’re like on death’s door. So is Blastocystis pathogenic or not? Well yes and no, it depends on what’s happening in the host. Depends on the internal environment of the gut, and the innate immunity of that person. As usual it’s a lot more gray than we’d like it to be.
Just a little personal story here, lately I’ve been overworking. Between my very full practice, and the blog, and facebook and twitter, and I’m spending a lot of time on this healthy baby product which I’m really excited about, it’s gonna be ready soon. I’m just like, I’m working too much, there’s no other way to put it, not taking my own advice. I have been exercising, doing my sitting practice, those pretty much are bulletproof, they never go away, but a lot of the other things I usually do to keep my brain functioning well, like just resting, surfing, going out in the sun, listening to music, doing yoga and other stress management stuff, having fun, watching a funny TV show or movie or something like that. I havn’t been doing that stuff.
DANNY RODDY: You better watch out cause Durian Rider is gonna write a post about you like he did Robb. Did you see that?
CHRIS KRESSER: No I don’t pay attention to that stuff.
DANNY RODDY: Well no doubt he’s crazy but he wrote a really mean article about Robb and then Robb responded with something really funny but I don’t remember what it was.
CHRIS KRESSER: I try to take the high road with that stuff, I don’t even have time to bother with those people. So anyways I was noticing a flare up in gut symptoms, ya know I have this history of digestive issues from when I got parasites and amoebas and a bunch of other stuff in Asia a long time ago, some of you know that story. I was starting to have gut symptoms, I hadn’t made a single change in my diet, a single change in the supplement regime (which is pretty minimal anyways), nothing else had changed except for the level of work I was doing and the amount of time I was spending taking care of myself so I switched some things up over the past week or ten days and even in that short period of time I’ve noticed huge differences, I feel like I’m back on my normal track again, so just a little cautionary tale.
Okay so what are the symptoms of a brain-gut axis problem? Well, fatigue and brain fog are a big indicator. We’ve talked about chronic digestive problems and especially those that don’t respond to dietary changes. Then we have things like progressive cognitive decline or memory problems, which we see in the elderly of course, but also an increasingly large number of twenty-five year olds. I have so many people in their twenties and thirties who are losing brain function, which is just kinda scary. It’s something that you don’t want to be happening when you’re twenty five years old. Anxiety, depression, ADHD, autism spectrum disorder, behavioral problems, and then here’s an interesting one, cold hands and feet. Especially if you have toenail fungus, because what’s happening there is that you’ve got reduced blood flow, reduced circulation to your peripheral tissues and the brain when you think about it is a peripheral organ. So, cold hands and feet, and toenail fungus can be an indicator of a brain-gut axis problem. I see that a lot actually, in my practice.
DANNY RODDY: Does it have anything to do with the thyroid? and the brain down-regulating things?
CHRIS KRESSER: It could, it could also just be a simple result of reduced blood flow. And that can happen in all kinds of inflammatory processes. So the basic physiology here is that in the brain the key players (in this gut-brain axis) are the frontal cortex, the insular cortex, the vagal motor nuclei (which I’ve already talked about) and the hypothalamus. The frontal cortex basically stimulates the vagal nuclei to activate gut motility (intestinal peristalsis), which is what moves the contents of our gut through the digestive tract and out the other end, and enzyme secretion. The insular cortex contains the somatotopic map, which is basically what lets the brain know where the gut is. And then the vagal motor nuclei activate intestinal motility, and they modulate blood flow, which we just talked about, but in this case to the gut. And then the activate the release of hydrochloric acid and digestive enzymes. The brain primarily communicates with the gut via neuronal projections and then hormones that are secreted via the hypothalamus. But in the gut the key players are the enteric nervous system, the intestinal immune system, which is the gut-associated lymphoid tissue and the gut flora, and then the intestinal microglia.
The enteric nervous system is really interesting actually, the gut is basically one big nervous tissue. In fact it’s been referred to as the second brain. There’s a book by that title by Dr. Michael Gershon that’s kind of interesting, it has some flaws but it’s worth reading. The enteric nervous system also generates intestinal motility and enzyme release and then it provides incoming input to the vagus nerve. Someone asked about serotonin in the questions and how much serotonin is in the gut, well 80% of total serotonin in the body is located in the enterochromaffin cells in the gut and this is used primarily to regulate peristalsis and motility. So this is why constipation and depression so often tend to go together. And then the remaining 20% is synthesized in serotonergic
neurons in the central nervous system that regulate mood and appetite, sleep, and muscle contraction, and a whole bunch of other stuff. So the gut communicates with the brain via cytokines and gut opiates and gut peptides like neurotensin and substance-P. Whew. Okay. Everyone who just zoned out for the last five minutes staring out the window while your driving or whatever you can come back now cause we’re gonna talk about some practical applications but I feel like it’s important to understand the basic physiology so that what we’re gonna talk about next makes more sense. Any questions Danny? How you doin?
DANNY RODDY: I’m good.
CHRIS KRESSER: You’re still with us, in your rotten meat smelling garage?
DANNY RODDY: Luckily the smell has subsided, it was bad man.
CHRIS KRESSER: Good. Okay so, how does the brain affect the gut. Well I know everybody’s experienced this in a very personal way, we have phrases like ‘butterflies in the stomach’ and ‘gut feeling’ that of course suggests the connections have been known for a long time. Maybe we all know somebody that has lost complete bowel control in a state of extreme fear or stress, certainly that’s in the movies and we hear about that sort of thing. But what are some of the mechanisms here. Well, in the intestinal mucosa there are blood vessels that are influenced by the autonomic nervous system. The intestinal mucosa also is infiltrated by the myenteric plexus which is a network of nerve fibers and neuron cell bodies that are in turn influenced by the brain. So as I said before the gut’s basically one big nervous tissue. I think I mentioned this study in a previous podcast or in an article but it was a really interesting study where they induced traumatic brain injury in mice, which is not too nice, but these mice developed leaky gut in less than six hours after having this brain injury. Even more interestingly if the researches stimulated the vagus nerve, which mimics increasing the brain output into the vagus, that actually prevented the leaky gut from developing.
DANNY RODDY: When they did that to the mice, is the root cause like, the brain injury causes stress?
CHRIS KRESSER: It causes decreased output into the vagus, cause remember I said before 90% of the output of the brain goes into the pontomedullary area and then into the vagus. A traumatic brain injury is gonna reduce that output and then they showed that by just stimulating the vagus, which mimics increasing the output, they were able to prevent a leaky gut. So they basically showed, proved that connection between the brain and the vagus and the gut.
Then you have other studies that show that neurotransmitters like serotonin and acetylcholine are involved in preventing or promoting ulcers in the digestive tract. And that alterations in the brain can cause abnormal gastric enzyme secretion. So I wanna talk about a few different studies that I have found over the last couple of years that I think are pretty interesting.
There was one published last year in the National Review of Gastroenterology & Hepatology and I’ll quote from the conclusion. It said “IBS is thought to be the result of disturbed neural function along the gut-brain axis.” So that makes it pretty clear.
DANNY RODDY: That’s big news.
CHRIS KRESSER: Yeah, there’s an interesting thing here where for a lot of years doctors told people with IBS it was all in their head. And that’s really not a nice thing to say, but it’s true. The thing is it’s not true in the way that the doctors meant it. You know what I’m saying? They meant you just need to get over this, or you’re just imagining it is what they meant. But what is true is that it is in your head, cause that’s where your brain is. And if the gut is malfunctioning then the brain is involved, and vice-versa. So it is all in our head but not in the sense that we’re to blame for it or we’re just making it up.
Another study in 2005 found that IBS patients have increased activation of pain circuits and decreased activation of pain inhibition circuits. So this is interesting cause, I don’t know if you remember this but when we had Kurt Harris on we were talking about fructose malabsorption and the gas that produces, and the difference in the way that’s experienced with people with IBS and people without IBS. And they found in that study that people with IBS and without IBS had the same amount of gas produced with fructose malabsorption, but it didn’t even bother the people who didn’t have IBS. It only was painful and uncomfortable in people with IBS. And so that’s what this is about here, people with IBS have a decreased pain threshold, increased activation of pain circuits and then decreased ability to turn off the pain circuits.
DANNY RODDY: So they’re just in a hyper-sensitive state?
CHRIS KRESSER: Exactly. Yeah, so it’s not even necessarily the amount of gas that’s produced, it’s how they experience it. And again it’s not their fault, it’s not something that they are imagining it’s a real neuro-physiological pathway. Journal of Clinical Psychiatry 2001, this is crazy, 50-90% of IBS patients seeking treatment have a psychiatric disorder. Woah. This includes panic disorder, anxiety, social phobia, PTSD or a major depressive disorder. I mean, if that doesn’t sum it all up, give you some strong evidence for an association between the gut-brain connection I don’t know what does.
DANNY RODDY: I hate to put you on the spot here but is there a figure for how many Americans suffer from IBS? It seems pretty common, at least among my peers.
CHRIS KRESSER: The only figure that stuck in my mind about that it’s now the second leading cause of people missing work, behind the common cold. That stuck in me more than whatever the number of millions of people are that have it. It’s causing serious debility and morbidity in the population. It’s right up there with depression in terms of how common it is and how debilitating it is.
DANNY RODDY: And then the third cause just being a normal hangover?
CHRIS KRESSER: And hating their jobs. Okay Biological Psychiatry 2009 they again not very nicely exposed rats to stress by separating them from their mothers early on in their life, and then they challenge them with lipopolysaccharide which is a bacterial endoxtoxin. And the rats that were exposed to the early life stress had increased pain and alteration in their gut flora compared to controls and the conclusion by the researchers was that early life stress alters the gut-brain axis, and in a permanent way, and causes depression, IBD, and IBS. I mean permanent I don’t know, they were suggesting that it’s something that wasn’t passing, it didn’t just last for the early part of the life for these rats, it persisted throughout their life. Whether that’s permanent for humans or can be reversed that’s a whole other question.
DANNY RODDY: Because mice, their lives are so much shorter could they say that it wouldn’t be transferable over to humans because we live so much longer? Would that have anything to do with it?
CHRIS KRESSER: Yeah I dunno, I think this all sort of, fairly gray territory in terms of earlier on it was thought that certain neurological conditions were irreversible and certain neural-pathways once developed couldn’t be undeveloped, but now more recent research suggests there is a lot more plasticity in the brain and in the nervous system than we thought there was, which means that it’s possible to form new connections and for those new connections to take over in terms of importance in the brain and nervous system. My sense is, that significant trauma early on in life probably would predispose somebody for life to certain, to maybe having a sensitive gut-brain axis. And maybe that sensitivity wouldn’t be reversible but by learning strategies for how to cope with it and things to do that manage it they can live a perfectly healthy, happy, normal life. That’s my sense but there’s nothing particularly scientific about that.
Journal of Neurotrauma in 2009 they found that traumatic brain injury can cause gastrointestinal disfunction, we already talked about this, and leaky gut. And then a study in Lancet found that patients with inflammatory bowel disease, which includes chron’s and ulcerative colitis, had focal white matter lesions which are these small areas of dead cells in the brain, with almost the same frequency as patients with multiple sclerosis. So how’s that. Once again extremely clear connection between brain issues and gut issues.
Now we’re gonna talk a little bit about how the gut affects the brain. There’s a lot of different mechanisms here and we only have time to review a couple of the main ones. Our friend Mat Lalonde actually sent me me a study a couple weeks ago that was just published that the gut flora influences the development of behavior and causes neurochemical changes in the brain. So again from the conclusion they said “we conclude that the presence or absence of conventional intestinal microbiota influences the development of behavior and is accompanied by neurochemical changes in the brain.” And they point out that even sub-clinical doses, small doses of pathogenic bacteria infused into the gut of mice can produce anxiety without any overt gut inflammation. So what they’re saying here basically is that the gut flora can not only affect how we digest food and whether our gut lining is permeable, but can actually influence the development of our behavior and one can even argue personality.
DANNY RODDY: I think it was Gershon that said have you ever met somebody with IBS that’s not anxiety prone. I think he said if you were a changed to a toilet you probably wouldn’t be in the best spirits either.
CHRIS KRESSER: That’s a vivid example for sure. Yeah, it reminds me of the fact that bacteria outnumber human cells in the body by 10 to 1. We have a hundred trillion bacteria in our gut that’s 1014, it’s just like an incomprehensible number. And so if you look at it that way you could say that we’re more bacterial than we are human. When you consider it that way it’s not that surprising that the composition of the gut flora can have so many effects on everything from our metabolism to our behavior. So another study by Lee, et al. found that changes in gut bacteria induced by feeding different types of food to mice altered their memory and learning. So they fed half the mice standard rat chow, and then the other lucky half of the mice got a 50-50 blend of rat chow and ground beef. And then they measured the diversity of the gut flora and the mice that ate the beef had significantly more diverse gut flora and significantly higher learning and memory scores. So now we’re talking about healthy gut flora making you more intelligent, essentially.
DANNY RODDY: Like serotonin in the gut, does acetylcholine, could that have somehow been involved? I mean I know we don’t have all the answers…
CHRIS KRESSER: I don’t know the answer to that Danny, actually where the majority of acetylcholine is produced. I don’t think it’s in the gut but I’m not sure.
One of the most interesting examples of how the gut affects the brain is this immune inflammatory cytokine model of depression, and I wanna get Dr. Emily Deans to come on the show and talk about this cause she writes a lot about it and she probably knows a ton more about it than I do. But I’m gonna give you my understanding of it. I like it because it’s the only model of depression that bridges the gap between physical and mental. We talked about this before, in Chinese medicine they don’t see depression as a mental problem they see it as a whole body problem. Mental, emotional, psycho-spiritual, physiological problem. But the immune inflammatory cytokine model from this perspective depression isn’t so much a disease as it is a sign of chronic immune system activation. And that chronic immune activation produces inflammatory cytokines that in turn produce depression I explained that back at the beginning of the show how that works. And this was discovered back in the 80s, that inflammatory cytokines have a huge effect on mood and behavior and you would have thought this would have had a gigantic impact cause it completely changes the way we look at depression. But it didn’t receive much attention at all in the mainstream press or the conventional medical world I suspect because there were no drugs available for treating it in this particular way. But the inflammatory cytokines that are associated with depression include interferon-alpha, tumor necrosis factor, interleukin-1 and 2, and it’s important to note that elevated cytokines don’t produce depression in everybody and why some people are susceptible and others aren’t isn’t really known. But we do know that inflammatory cytokines produce symptoms of depression in some people. And the best example of this is patients given interferon treatment for hepatitis. I don’t know if you’ve ever heard about this Danny, but interferon is a nasty, nasty drug and basically the idea is to increase the inflammatory response so that the body can deal with the hepatitis and most of the patients who take this drug, they report severe fatigue, complete lack of interest in life, lack of concentration, and just debilitating depression. And suicide rates are higher on interferon than any other drug. In fact one study 65% of patients taking interferon became psychiatric patients during the study.
DANNY RODDY: Holy smokes.
CHRIS KRESSER: Yeah. And the depression didn’t stop immediately after stopping the treatment. So definitely a strong connection between inflammatory cytokines and depression. We also know that depressed people secrete greater quantities of inflammatory cytokines than normal people and this has been extensively studied by… Dr. Michael Maes and his colleagues in Belgium, and they’ve published like 40 papers demonstrating that chronic immune activation and the associated increase in cytokine production is characteristic of depression. So you have all those different ways that the gut can affect the brain and particularly inflammation in the gut can cause inflammation in the brain. So the takeaway here is that anxiety and stress and IBS and IBD, the gut and the brain, they’re all part of the same axis, they always go together. Every stressful event that we experience in life increases the plasticity of stress pathways in the brain which means it makes the brain essentially more efficient at running stress pathways. And there’s a saying in functional medicine, fire in the gut, fire in the brain. Which sums it up pretty well. Digestive function will start to fail immediately after the brain starts to fail, and the inter intestinal gut mucosa in the brain themselves don’t have any pain fibers which is why brain-gut, you don’t see people coming into the clinic going my brain hurts. My brain feels really inflamed can you help me? They come in saying I can’t eat any foods, I’ve got gas and bloating, I can’t remember anything, I used to be able to concentrate for long periods and now I can’t, I’ve got cold hands and feet, and I’ve got this toenail fungus and it won’t go away, this is what people say when they’ve got a gut-brain issue. And as a patient or a clinician if you ignore the role of the brain in addressing gut issues, success is definitely gonna be limited. Probiotics, and HCL, and diet are all very important of course. But it’s possible to do all of that right and still have gut symptoms as I’ve experienced directly myself, and as a lot of my patient’s have experienced. So this is one of the reasons that I’m always harping on the importance of sleep, and stress management, and cultivating pleasure, because these are all things that we can do to help our brain function better.
So let’s talk a little bit more about that. You have a question?
DANNY RODDY: No, I liked your conclusion.
CHRIS KRESSER: Okay, good. So there’s three things that the brain needs, essentially. Glucose, oxygen, and stimulation. As far as stimulation goes that’s why people that stay mentally active as they get older tend to age better. And do a lot better than people who don’t, you know who just sit on the couch and eat jellybeans and watch TV. And this is another reason why blood sugar regulation is so important. When people come to see me in the clinic, the first things that I’m looking for are oxygen deliverability and blood sugar regulation, those are like, the two deal breakers. Once again here as we talk about the brain we see glucose and oxygen being two of the main things that it needs. Alzheimer’s and parkinson’s and other neurological conditions have been called diabetes of the brain, that’s one of the newer theories about it and of course this also illustrates why stress management is so important. Studies show that cortisol rhythm maintains blood sugar stability, so if cortisol doesn’t go down you get insulin resistance and if it goes too low and can’t come up you get hypoglycemia, which is a total disaster for the brain. And then we know that elevated cortisol also damages the hippocampus. And that chronic stress atrophies the brain, it literally atrophies the brain. And this is also why blood flow to the brain is so crucial because blood carries oxygen and glucose and everything else we need to the brain. You could almost say that blood flow equals function.
So two of the best ways to increase blood flow to the brain are exercise and acupuncture. And actually I wrote a whole series about, I believe that one of the main reasons that acupuncture works is that it increases blood flow. That’s kind of a western understanding of how it works but there’s a lot of support for that. And it’s been proven to increase blood flow to the brain. And so anyone with a brain-gut axis issue should definitely be trying acupuncture on a pretty regular basis. And then there are certain nutrients and botanicals like feverfew, ginko, cayenne, and then some limited research suggests that vinpocetine from periwinkle can increase blood flow to the brain. And then you of course would have to deal with any anemias that are present, which of course is compromised oxygen deliverability. The impaired ability of hemoglobin to deliver oxygen to the tissues including the brain. I think anemia is one of the most under diagnosed and misdiagnosed conditions there is, cause I see anemias in 30-40% of my patients and they’re almost all unaware that they have it, and their doctors havn’t told them anything about having it. If they see low hemoglobin they just give them iron, even if iron deficiency is not the cause of anemia but that’s a whole other issue. And then stress management, stress management, stress management. It just keeps coming back to this. Things like mindfulness based stress reduction, Jon Kabot-Zinn’s programs, Feldenkrais, yoga, qi gong or tai chi, whatever it is for you. Different people have different things that work for them. It’s super important to integrate this into your life. You notice that I’m not staying stress reduction, or stress elimination because in the modern world most of us don’t have that luxury or option. Stress management is the key.
Regarding the gut we’ve talked more about this in other podcasts, but a gut-healing protocol might include the GAPS diet, glycine rich bone broths, probiotics, prebiotic foods like sweet potatoes, jerusalem artichokes, stuff like that. And then you’ve got botanicals like marshmallow root, and slippery elm, and chamomile, and spanish moss can be helpful. And if there’s a pathogen you should address that. But really at least in terms of this episode I’m focusing more on the brain because I think that’s the part that people are missing more. There’s a lot out there on how to heal the gut but not that much on how to heal the brain.
And I mentioned before that when the microglial cells become activated it’s hard to turn them off. There are some nutrients that have been demonstrated to do that including curcumins like turmeric, skullcap, green tea extract. In terms of healing the blood-brain barrier you’ve got alpha-lipoic acid, glutathione, which you need to take things that help glutathione synthesis, you can’t take just oral glutathione it’s not effective. And then the omega 6:omega 3 balance is absolutely crucial in blood-brain barrier integrity. Don’t go out and just buy all this stuff and come home with a shopping bag of supplements, try to find someone who can help with this and focus your efforts. It’s definitely worth doing because it’s a really important pattern to manage.
DANNY RODDY: Like Spectracell will actually measure the amount of glutathione in your blood correct?
CHRIS KRESSER: I don’t know about that test.
DANNY RODDY: I don’t know if it’s totally bunk or not, but I remember receiving it, and they didn’t tell me that it measured it but I got it back and it was cool.
CHRIS KRESSER: I’m always naturally skeptical, as you might imagine, of those kind of tests. but anyways I don’t know anything about it so I can’t really say. So let’s take a couple questions, I know we had a long episode last time I don’t wanna go too far this time, but let’s take a few questions and then I have a couple things to end with.
DANNY RODDY: Alright cool, this one I believe was on your facebook page, from Stephanie Alexander. I would like to understand the connection between acute emotional stress and the onset of gut issues, and the progression to additional health issues.
CHRIS KRESSER: Okay well I think probably we’ve covered that mostly but early studies suggested that a stressful evert would trigger hormonal and neuronal reflexes in the brain that influence the gut, and that does happen but recent reports have also shown that the gut produces the same stress peptides that are present in the brain and the central nervous system. These peptides regulate intestinal motility which is the rate at which digested material passes through the intestines. So we’re getting back to that extreme fear stress event that causes diarrhea. During a stressful event the normal amount of those peptides gets totally thrown out of whack and that affects digestion and motility. And when that happens repeatedly over time it can evolve into a gut-brain axis disorder like IBS or IBD.
DANNY RODDY: Awesome, the next question, kind of a two-pronged question from Lisa Rose. I would love to hear your take on probiotics. Should everyone be taking them? or can it do more harm for some. Which brands do you recommend? And the roll enzymes play to help digest food while the gut heals, also highlighting the power of foods for a healthy gut, like fermented foods. What other foods help? And then an additional question from Laura that’s kind of in the same vain, should people with healthy gut digestion take probiotics? What happens if you take too much? How do you determine the right amount?
CHRIS KRESSER: I don’t see any need for healthy people to take probiotic supplements but I think incorporating fermented foods into your diet is a good idea for everybody. Number one it tends to help with digestion, number two it can just help normalize the gut flora and protect us against overgrowth of pathogenic bacteria or parasites that we might take in through food, and number three they’re tasty and I like them. Number four they tend actually to have even more microorganisms in them than a lot of the commercially available probiotics. Number five I think some common sense and maybe studies suggest that they are more likely to survive the stomach acid and make it to the colon which is where they’re needed. So, I don’t typically recommend probiotic supplements as a matter of course, I do recommend probiotic foods so we’re talking about dairy ferments like kefir, yogurt, and creme fraiche, fermented cream which basically is creme fraiche but there are different ways to do it. And then you’ve got fermented vegetables like kimchee and sauerkraut, and saueruben and fermented beverages like beet kvass. There’s a great book called Wild Fermentation by Sandor Katz that has like, every possible fermented food you can imagine and how to make it. Full Moon Feast by Jessica Prentice is really great for that too, as is Nourishing Traditions by Sally Fallon from the Weston A. Price Foundation.
DANNY RODDY: Yeah food not pills.
CHRIS KRESSER: Yeah but I use probiotics and prebiotics therapeutically in my practice for sure, because for some people the food doesn’t seem to be enough.
DANNY RODDY: Totally. Okay the next one’s gonna be from Mike Zemrose, please discuss psychosomatic reactions to food and how this complicates diagnosis of gut related problems.
CHRIS KRESSER: I’m not totally sure what he means by psychosomatic reactions to food but I’ll take a guess. The Chinese have a great saying, I think I mentioned this before when I wrote the article on the 80/20 rule, which is that it’s better to eat the wrong food with the right attitude than the right food with the wrong attitude. And of course it’s best to eat the right food with the right attitude, but that’s not always possible or it doesn’t always happen that way. And this is in part why I do suggest an 80/20 rule or 90/10 rule for most people and for those of you who don’t know what that is, that means that 80 or 90% of the time you eat a paleo plus raw dairy type of diet, or whatever you wanna call it, Perfect Health Diet, Paleo 2.0. And then the other 10-20% of the time you eat whatever you want. And for a lot of people whatever they want still just is the paleo type of diet, but some people might have a food that they really associate with happy times, when they were a kid, or they’re out with friends and they wanna get some ice cream, or whatever. And the pleasure that that experience can create, and the stress and feeling of deprivation and stuff that that can prevent will actually, according to this Chinese saying is actually better, will have a more beneficial effect on the body. So I think that’s a good rule to follow if you’re generally healthy. If you’re gluten intolerant or celiac for example you don’t get the 80/20 rule with gluten, with bread. It’s 100%/0, you never get to have it. Anyways back to the question, there was an interesting study where they hypnotized patients and put them into four different emotional states. Relaxation, anger, happiness, or excitement. And then they observed the gut after they ate. Relaxation and happiness increased the distension volume required to produce discomfort meaning that, going back to what we were talking about IBS and hypersensitivity that when people are relaxed and happy they’re less likely to experience discomfort while eating. And then when the patients were angry it decreased the distension volume that was required to produced discomfort. So I don’t think this is a surprise to anybody that when you’re happy and relaxed you’re gonna digest your food better, when you’re angry you’re not. But it’s definitely in the scientific literature.
How we feel when we eat alters the secretion of hormones and peptides and neurotransmitters, and that effects not only our digestive function but also things like cardiovascular function. Dr. Malcolm Kendrick talks about this and he points to some studies in his book The Cholesterol Con, that postprandial or after meal stress is one of the most significant risk factors for heart attack. So those French that have those leisurely two hour meals, they know what they’re doing. Whereas here we eat, and we’re eating in front of the computer, or we’re chomping down an egg mcmuffin while we’re changing lanes on the freeway or whatever. That’s kind of a disaster.
DANNY RODDY: Well speaking of the French, our next question is from Pierre Brode. His question is I’m interested in how stress eating throws off the physiology/ body chemistry and how the brain-gut axis amplifies it, and what are some ways of resetting it caught in the cycle. Big question.
CHRIS KRESSER: I think we’ve hopefully covered this during the podcast, but I’ll just mention a few… stress eating we havn’t talked about particularly. Sugar and carbs and fat can mitigate the effects of stress via increasing opiates and dopamine, other neurotransmitters like serotonin that make us feel good, feel like life’s okay and everything’s gonna be fine. But if you do this regularly during times of stress you can cause adaptations in those pathways that can lead to overeating. Other studies have shown that food reward and sensitivity is decreased during stress, which leads to overeating. In other words when you’re really stressed out you don’t actually enjoy the food that you’re eating as much as you do when you’re not. And then you keep eating because you’re not getting that food reward that you’re expecting. And then, I don’t know if you saw this but Stephan Guyenet over at Whole Health Source wrote a post today about food reward. It showed that mice eating chocolate ensure but not vanilla or strawberry ensure, these are these elemental diet drinks that they give people that are just disgusting I can’t believe that mice would even eat them at all, it’s surprising to me. But the mice eating the chocolate ensure could overeat and become obese, whereas the ones eating strawberry and vanilla didn’t. So what this suggested was that the flavor of food actually influences body fat and body fat set point. And then the last thing is, I guess we talked about this before but elevated cortisol can lead to increased food intake. That’s an evolutionary mechanism probably designed to make sure that we get enough food to fuel our metabolic needs during times of stress or maybe when a food shortage is on the way or something like that. So the way to deal with this, is as I said to take steps to manage stress throughout the day and throughout the week and to find other ways of coping with stress when it becomes overwhelming aside from eating. That’s a topic beyond the scope, we can’t cover that in significant detail right now at the end of the show. But I think the key is to manage stress regularly so that you don’t get to that place where you’re just so overwhelmed that the only solution is a half of a chocolate cake.
DANNY RODDY: Cool Chris, do you have anything else to throw in about the gut-brain axis?
CHRIS KRESSER: I don’t think so, did I miss anything? I’m sure I did.
DANNY RODDY: No I thought it was fantastic, you covered everything.
CHRIS KRESSER: Well I wanna talk a little bit about this healthy baby home study course that’s coming out soon. I’m super excited about it, we actually renamed it it’s now called the Healthy Baby Code. Very secret code.
DANNY RODDY: That makes me think of the History Channel’s Bible Code that I used to watch in high school.
CHRIS KRESSER: The Da Vinici code? No it doesn’t have anything to do with that. It’s based on, I was giving these live presentations, for those of you who aren’t aware of this, on nutrition for fertility, and pregnancy and breastfeeding. And they sold out, there was huge demand for them locally, and a lot of people on my blog and facebook and twitter were asking if I could make it available to people who didn’t live locally here in the bay area. It’s a super important topic, I feel really passionate about getting the information out there so what I did is I turned the presentation, which was about three hours, into this home study course. I actually expanded it considerably, and there’s gonna be six video modules that are like screencasts from the presentation, covering things like the basics on how proper nutrition contributes to the lifelong health of your baby, which I just wrote a blogpost on called the developmental origins theory. The sacred fertility foods that have been used by traditional cultures around the world. And then module two we talk about macronutrients, protein, fat and carbohydrate. Not necessarily how much of each but what type of each which I wrote about in my 9 steps series and Kurt’s talked about a lot. Find out which types of fat and carbohydrate and protein are best for you and your baby. And we talk about micronutrients, essential vitamins and minerals, which ones are critical during the developmental period, during pregnancy, and also for fertility. Where to find them in foods and when it’s necessary to supplement and what dosage of each you might need to supplement with. And then in module four we talk about food toxins, we learn about the four neolithic agents of disease which I’m sure many of you are already familiar with. Cereal grains, industrial seed oils, excess fructose and soy, modern processed soy. And then in module five we talk about breastfeeding and first foods, which a lot of people have questions about. How long should you breastfeed, when should you introduce foods, and how do you introduce them safely to try to minimize the risk of food allergies and reactions, autoimmune conditions and stuff like that. And then in module six we kind of put everything together and into a focused strategy for really supercharging your fertility and promoting healthy pregnancy and then raising a vibrant, healthy, beautiful baby. Of course this is very, my personal motivation for doing this too because my wife is six months pregnant, we’re expecting a baby in july and we had kind of a long road, difficulty conceiving at first. My wife has autoimmune thyroid disease and a lot of doctors just told us not even to bother. Of course that didn’t sit well with me so, I did tons and tons of research in my typical obsessive compulsive way, into what nutrients were really necessary to support a healthy pregnancy and the magic happened last october and we conceived so I’m really excited to share this with people. In addition to the video modules which are by the way gonna be transcribed into pdf’s cause I know some people don’t like video and they learn better by reading, I happen to be one of them. And then there’ll also be MP3 recordings of each module so if you drive a lot and you wanna listen to them in the car you can do that.
And then I’ve added a whole bunch of bonus stuff which we’re excited about. There will be quick reference charts, an easy to follow nutrient chart that lists all the essential nutrients and what foods they’re in and what dose to supplement with if you need to. There’ll be a two week meal plan, which both my wife and I worked pretty hard on from collecting recipes from places like health bent and the cheese slave and the paleo diet lifestyle, a lot of great recipes on the web and then our own recipes, we’re not too shabby cooks ourselves. And then there’s gonna be an interview, of frequently asked questions with me, some of the most frequently asked questions about nutrition for fertility, pregnancy and breastfeeding. There’s gonna be a list of recommended supplement brands, dosages. And then of course it wouldn’t be complete without come stress management, because that’s obviously a huge factor for women trying to get pregnant and women who are pregnant. My wife, Elanne is a Feldenkrais practitioner and has also done a lot of somatic experiencing training which is a particular approach to dealing with stress and trauma. So she is recording some stress management audio programs for women who are trying to get pregnant and men for that matter, and women who are pregnant and breastfeeding. So that’s the whole kit, and now you can see why I’ve been working so hard.
DANNY RODDY: No doubt.
CHRIS KRESSER: So that’s gonna hopefully be available in like, I want it to be available in two weeks but maybe more realistically three weeks and please don’t shoot me if it’s the end of may. I’m working as hard as I can to get it out there. So if you’re not already on the list for this you should go to growahealthybaby.com that’s the old name for it but that’s where the sign up list is and I know it’s a little but confusing, it’s kind of in transition to the new name but if you go to growahealthybaby.com you can sign up to be on the email list, be notified when it’s released, and one reason to be on that list is that I’m gonna be making a special offer to people that are on that list. We’re gonna do kinda like a beta launch, a smaller launch just to that list. Kick the tires a little bit, and in exchange for people’s feedback I’m gonna offer some pretty cool stuff to people on that list so make sure to join that if you’re interested in this and pass the word on to folks that you think might be interested.
DANNY RODDY: Awesome you can find all my insanity at Dannyroddy.com, keep sending us your questions at thehealthyskeptic.org using the podcast submission link. Chris, what a great episode, thanks.
CHRIS KRESSER: Yeah I had fun, thanks everyone we’ll talk to you next week? are we doing, is it Stephan?
DANNY RODDY: May 20th is Masterjohn.
CHRIS KRESSER: We’ve got some exciting episodes coming up we’ve got Chris Masterjohn, we’re gonna bring cholesterol into the 21st century finally. It’s gonna be like the fully up to date, integrated understanding of cholesterol, all the latest research and cut through the hype and the confusion and you’re finally gonna understand this whole cholesterol thing. And then Stephan Guyenet is gonna come back and make a second appearance, we kicked the whole podcast off with him talking about obesity and he has some very interesting, newly developed theories about obesity and weight regulation that he is gonna share with us which I’m super excited about so, looking forward to that.
DANNY RODDY: Awesome, cool. That brings us to the end of the episode, take care guys.
CHRIS KRESSER: Alright, see ya later, take care of your brain-gut!
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