The Dr. Hyman Show - Is Brain Inflammation The Cause of Depression, Dementia, ADD, And Autism? A Functional Medicine Approach To Neuroinflammation with Dr. Todd LePine

Starting point is 00:00:00 Coming up on this episode of The Doctor's Pharmacy. Depression is not about serotonin. Yes, you know, serotonin is an important neurotransmitter, but a large part of depression is actually related to neuroinflammation. Hey everyone, it's Dr. Mark Hyman. People always tell me they miss wraps and they miss sandwiches for lunch, and they're looking for a great alternative. Well, I found one, and it won't sabotage your health. They're called organic coconut wraps and they can replace bread and

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Starting point is 00:01:58 but even when we eat super well, most of us are missing out on certain essential nutrients. Our soils have become depleted and our digestive tracts just aren't working so great. They're compromised by stress and toxins and they just can't absorb nutrients as efficiently as they should. And that's why I always use, and I recommend to my patients, a multivitamin mineral as nutritional insurance. It covers the basics for all our day-to-day body functions, all the things that we need that our food might be missing. But there are so many products out there I wouldn't go near because they contain artificial fillers or inactive ingredients,

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Starting point is 00:04:08 Athletic Greens can make in your daily wellness routine. Again, that's athleticgreens.com forward slash Hyman. Now let's get back to this week's episode of The Doctor's Pharmacy. Welcome to The Doctor's Pharmacy. I'm Dr. Mark Hyman and that's Pharmacy with an F, a place where conversation doesn't matter. If you care about your brain, you better listen up because we're going to talk about the brain on fire today, which is the cause of so many mood disorders, neurodegenerative disorders like Parkinson's and Alzheimer's, even things like autism and ADD.

Starting point is 00:04:42 We're going to learn about how the brain gets on fire, why it gets on fire, and what you can do about it from a functional medicine perspective, because we are not succeeding with these conditions in traditional medicine very well. And we're going to hear about why on this special episode of House Call from the doctor's pharmacy with Todd Lepine. Again, one of my great docs from the Ultra Wellness Center. We've been working together for, gosh, almost 30 years now. And we see so much of this, Todd. Todd is a graduate from Dartmouth. He's an incredible physician.

Starting point is 00:05:14 He's a lecturer and teacher all over the world in the field of functional medicine. And he is just one of the smartest dudes I know in this space. So welcome, Todd. Well, thanks, Mark. I'm excited to be talking this afternoon. Okay, so we're going to talk about the brain. And what's really been striking to me over the last few decades, and I first heard this, you know, from Dr. Perlmutter, who's a neurologist, which is that most brain diseases are diseases of brain inflammation.

Starting point is 00:05:37 But when the brain is inflamed, it doesn't hurt like your joints or, you know, a sore throat. hurt, like your joints or a sore throat, it creates all these other cognitive problems, whether it's depression, anxiety, autism, ADD, Alzheimer's, Parkinson's. These are all inflammatory diseases of the brain. So talk about how we think about the brain and how traditional medicine thinks about the brain in terms of how we approach the issue of inflammation. Well, you can even go back to our training, Mark, because I can remember when we were learning about the brain, it was all about learning about the neurons and the neural synapse. And the neural synapse are the two

Starting point is 00:06:21 nerves talk to each other, and there's millions of them. And it was all about understanding that and the neurotransmitters, you know, epinephrine and serotonin and dopamine. But what we're learning more is that the brain actually is not so much about the neuron, but it's about what I call the dark matter of the brain. Now, in physics, we know about dark matter. Most of the universe is actually dark matter. We can't really see it, and it's not there. And regular conventional medicine entirely misses the dark matter of the brain, which is really related to the glial cells. And this is really important. A lot of people have probably never heard of glial cells.

Starting point is 00:07:01 Glial cells actually come from the Latin term meaning glue. So it's the cells that hold the brain together. Only about 10% of the brain are composed of neurons and about 90% of the other cells in the brain are the glial cells. And the very important part of the brain that's related to neuroinflammation are what are called the microglial cells. And a lot of doctors probably forgot about this. They learned it in medical school and promptly forgot about it. But the microglial cells are the immune system part of the brain. And this is the part of the brain that gets activated under exposure to a bacteria, a fungi, a virus, or some type of pathogenic organism, or some type of foreign molecule. And when the brain gets activated via the microglial system, that causes neuroinflammation. And neuroinflammation is incredibly important. I mean,

Starting point is 00:08:01 a lot of the things that we see in our day-to-day practice, you mentioned it, depression. Depression is not about serotonin. Yes, you know, serotonin is an important neurotransmitter, but a large part of depression is actually related to neuroinflammation. In fact, studies have shown that people who have depression have a higher risk for dementia. So it's not just about a serotonin deficiency. And it's just like cholesterol is not, you know, that's not the big thing about heart disease. Heart disease is about inflammation. Neuroinflammation is about inflammation. It's not just about these single molecules like cholesterol and serotonin. So it's really

Starting point is 00:08:39 important to look at the whole big picture and how that relates to conditions that we see all the time. Things like Alzheimer's disease, things like ALS, things like multiple sclerosis, things like even schizophrenia. And actually I'll talk about some interesting vignettes about how schizophrenia is actually tied in with the neuroinflammation in the immune system. It's really quite fascinating stuff. And then there's the other thing, I don't see children, but pandas, I'm sure you have probably cases of patients who've had pandas, which is the pediatric autoimmune neuropsychiatric disorders related to strep infections. And this can be a devastating clinical scenario where all

Starting point is 00:09:27 of a sudden this young boy or girl starts getting these strange neurological type behaviors, these tics, these OCD type behaviors, et cetera. And these things are driven by neuroinflammation that the original description was that it was due to a strep infection. And, you know, mothers and fathers know about that because when a kid gets a sore throat, they take them to the doctor, make sure they don't get a strep infection. And typically we focused on strep being important because a strep infection can cause rheumatic heart disease. A strep infection can cause glomerulonephritis. That's why we're so on top of strep infections. But what doctors are missing, and even a lot of mainstream pediatricians are missing,

Starting point is 00:10:11 is that those strep infections, not only can they cause molecular mimicry where the molecules, when they're attacking the strep bacteria, what they'll do is those antibodies will actually start attacking the brain. And that's where we end up with these conditions like pandas. Yeah, it's just so remarkable, the research on the brain in the last decade and how it's revealed that all the conditions that we thought were maybe psychiatric are maybe more biological in the sense that they're disorders of brain immune function. And you mentioned the glial cells, which is the brain's immune system that cleans things up. But there's so many things that screw it up, including lack of sleep, which is a big one.

Starting point is 00:10:52 That's when it's really active. But I know I've seen in my practice that focusing on brain inflammation has led to the most miraculous cures for all sorts of, quote, incurable conditions. And it's not often easy to find what the cause is. I had a patient the other day who had tics since he was a little boy. And it turned out he was really, they came on after he had really bad series of strep infections. And I think, to my mind, he hasn't even been thought of having PANDAS, but he might have sort of this low-grade inflammatory response from the strep that's been going on for 30 or 40 years, but nobody picked it up. So we see all this kind of stuff, whether it's depression. And depression, you know, depression, you think, oh, that's a mood disorder.

Starting point is 00:11:33 Well, yeah, it is a mood disorder. And sometimes it's because, you know, you have a loss or some tragedy in your life. And usually that's sort of temporary. But these sort of chronic mood disorders are often related to brain inflammation. And they've even talked about using drugs for rheumatoid arthritis for depression to kind of shut off the inflammation of the brain. I think that's a bad idea. You know, what's causing all this brain inflammation that's leading to this sort of rampant epidemic of brain diseases? You know, I wrote a lot about this in the Ultramind Solution over a decade ago, and it's only, you you know increased in terms of the the prevalence of these problems and the data linking inflammation and and actually uncovering some of the causes

Starting point is 00:12:12 of inflammation that are driving this can can you talk about like what you know from a traditional perspective what we do is we give you medications we get antidepressants and we're not actually giving anti-inflammatories for alzheimer's although they tried giving people like advil and see what happens but it didn't work. So what is like the approach we take to finding out what the causes are? Well, that's where you really have to take time. And as you well know, we do a deep dive in listening to the history. And I think that's one of the things that probably distinguishes us when we do functional

Starting point is 00:12:42 medicine is we have the time and we take the time to actually listen and listen to the patient's story. And there's a saying in medicine, if you listen long enough, the patient will tell you what the problem is, but you have to allow the patient to talk and you have to be able to listen and piece together the puzzle. So it's really about mapping out the timeline of when did the patient's symptoms start? How old were they? What was happening around that time? Did they get a vaccination? Did they take an antibiotic? Were they bitten by a tick? Were they exposed to some kind of a toxin? Did they have dental work? I mean, there's all different kinds of things that can trigger inflammation. And that's where you really have to play medical detective. And, you know, sometimes you're going to find it on the first time. Sometimes you're not,

Starting point is 00:13:31 it might take you, you know, a lot of uncovering, you know, lifting up stones, leaving no stone unturned. And that's where a functional medicine approach where, you know, we do a lot of advanced testing to look for, you know, not necessarily an infection per se. It's not like you have a fever and you're sick, but what we would call a stealth infection, where you have a bacteria or a virus or an atypical bacteria present in the body that is causing this immune activation. And in the process of the immune activation, the brain gets inflamed and then can manifest as having a whole bunch of different types of neuropsychiatric conditions or potentially even memory issues or motor conditions or other neurological conditions like multiple sclerosis. So it's a real, you know, you have to play detective. It is. I mean, and the key things, you know, really drive the problems are the usual things we see that drive inflammation in general, whether it's autoimmune disease or anything else.

Starting point is 00:14:27 It's toxins. So it could be all the environmental toxins. We see this in Parkinson's with pesticides and chemicals. We see evidence of heavy metals playing a role in many of these brain disorders that drives inflammation as well as toxicity. We see the microbiome playing a huge role. I just recorded a podcast with Emmer and Mayer for the doctor's pharmacy, and he's all about the gut-immune connection and how it affects the brain and the gut-brain connection. And he's written a lot about the biology of this.

Starting point is 00:14:56 This is not some abstract idea. It's something that's really becoming fleshed out in literature and that people are coming to grips with as a force to be reckoned with in terms of the brain. And so we have to understand the microbiome's role, toxins, foods. For example, gluten can be very inflammatory for the brain for many, many people because it produces both inflammatory antibodies that affect the immune system and autoimmune disease, but also it can be a direct irritant in terms of the proteins that get digested and that flame the brain. And then, of course, there's infections that you were talking about, like viruses or tick infections and so forth. These all can be driving brain inflammation. So in functional

Starting point is 00:15:39 medicine, what we do is we go, wait a minute, what is the story behind this person's particular illness? As you said, we go into a deep history. And if we don't do that, we will miss often the real keys to figuring out the root cause of their problems. And that's really what's so beautiful about functional medicines. We have a set of tools and a set of therapies that allow us to, one, identify the causes and two, to actually treat them directly. And it's pretty exciting because we do see a lot of changes from people's health. Absolutely. And you were talking about, you know, the connection with the gut and there's really some fascinating stuff. You know, when I was in training, you know, we talked about Parkinson's and Parkinson's is the old, old person's disease. As you get,

Starting point is 00:16:17 as you get older, you slow down. And part of that slowing down is Parkinson-like features. But what we're finding out is that Parkinson's is a spectrum illness, and there is a big connection between patients who have Parkinson's and gut disruptions, leaky gut, gut dysbiosis with actually both bacteria and yeast. And there's a fascinating literature on the microbiome and the metabolites of the microbiome. And there's a woman whose husband has Parkinson's. And believe it or not, she actually diagnosed his Parkinson's by how he smelled, which is to say that when you eat certain food, the bacteria in the yeast actually do a metabolism of those foods and will produce these chemicals,

Starting point is 00:17:07 which are what we call the metabolome or the gut micrometabolome. And those metabolites in some people can affect the brain. And so in essence, you can sort of sniff out Parkinson's. And she actually did that. She actually could, she sensed that there was some something going on with him and then had him examined. And he was then diagnosed with Parkinson's. And in fact, they're actually training dogs to sniff out Parkinson's. Dogs can tell you if you're going to have a seizure or if you have a low blood sugar or if you have Parkinson's or cancer. It's pretty fascinating. I prescribe dogs all the time it's like it's one of my found my prescription absolutely yeah well it's interesting the body knows uh and i you know i think um maybe we can just sort of share as a way of illustrating the power of addressing

Starting point is 00:17:58 inflammation on the brain with some cases i have a bunch of cases from autism and Alzheimer's, but it'd be good to get sort of a sense from your experience. What are the things that show up and how did you treat it and what happened? Well, you know, I've had a whole variety of cases. In fact, a couple of cases that we've had at the clinic where we had some patients who presented to psychiatric hospitals. And when it came out, you know, when somebody has psychosis or a breakdown, if you will, they call that a psychotic break or a manic break or whatever you want to call that. And we've had a couple of recent cases where the patient's underlying trigger was Lyme disease, which is a spirochleic condition.

Starting point is 00:18:51 And I always remember, this is something that I really like to emphasize to my patients, is that way back when doctors used to treat syphilis. We don't have a lot of syphilis in private practice today. It's just, it's a condition which was readily treated and it's pretty much gone, although there's still some occurrences of it. But syphilis was caused by a, or is caused by a spirochetal bacteria. And that's the same thing as Lyme disease. And Lyme disease is the great mimicker. And it also can cause dementia and psychosis. So that's one of the conditions that trigger neuroinflammation.

Starting point is 00:19:30 And then also there was a recent case of Bartonella also causing neuropsychiatric conditions and a diagnosis of schizophrenia. So it's really a fascinating, fascinating field. And the problem is, is that psychiatrists are not trained to think this way. And neurologists are not trained to step over into psychiatry. So they're like, they're two different fields, but they're really the same field. So it's neuropsych, neuropsychiatry. This is an area that is actually really quite fascinating to me. And people always ask me, what kind of doctor are you? And I have my own description. Yeah, I can answer that question. connection between the brain, the gut, the immune system, and all of the body when it's all sort of interconnected. And it's really, really fascinating. And you can really help these people who are having significant conditions. So what happened? You said this patient

Starting point is 00:20:37 with schizophrenia, right? And you found the tick infections. What happened then? Were able to get their symptoms down by treating the underlying cause, which is the underlying spirochetal infection. I also had another patient who had a mycoplasma infection. And it's actually known in the literature, mycoplasma is an atypical bacteria. And it's another infection which can cause the brain to be on fire. So it's a really fascinating thing. And one of the tests that you can do that can check for this, it's not a common test, I don't know if you've done this, Mark, is the NMDA receptor antibody testing. This is looking at the parts of the brain that are stimulatory. And this is

Starting point is 00:21:29 something that any doctor who has a patient who has gone quote unquote crazy or had a psychotic break, they should have an NMDA receptor antibody test. Because if you have this, it tells you that there is some type of neuroinflammation that's driving their symptoms. Yeah, it's quite incredible. So I've had patients who have schizophrenia before or bipolar disease. And, you know, you think these problems are just so intractable and so difficult to treat. And they can be. But, you know, in fact, the whole field of functional medicine came out of the field of psychiatry with Abraham Hoffer's discovery that you could treat schizophrenia using nutrients and helping to

Starting point is 00:22:12 improve the biochemistry of the brain. And then Linus Collingwood's seminal paper, Orthomolecular Psychiatry and Science Magazine in 1969, which talked about the perspective of how do you straighten molecules? In other words, how do you correct the imbalances or dysfunctions in your biochemistry? That's called orthomolecular, which means to straighten. And that has really led to the whole field of functional medicine. And we then sort of expand on that with our understanding of the role of inflammation in the brain. And I, you know, many schizophrenic patients have high levels of, for example, gluten antibodies. About 20% of schizophrenics have anti-glycan antibodies in their bloodstream. When you take the gluten away, they do better.

Starting point is 00:22:51 That causes brain inflammation. And when you do autopsy studies on people with Alzheimer's or autism or schizophrenia or depression, you find that their brains are inflamed. So, you know, when you start to think about that, it's like, wait a minute, we are treating this completely incorrectly. And this is what was classical traditional medicine. You treat the symptoms, not the cause. And functional medicine is really about the cause and why, not just what disease you have, but why do you have it. And in the case of these brain disorders, it's often not obvious. And the problem may be far away from the brain. It might be in the gut or it might be in your diet or it might be a gut, or it might be in your diet, or it might be a toxin, or it might be an infection, or it might be mold. And it might be all sorts of things that we are kind of missing the boat on. And so we have this potential to sort

Starting point is 00:23:35 of rethink our whole approach to brain science. That's what's so exciting when we see the work of guys like Dale Bredesen or others, and nutritional psychiatrists like those at Harvard, and metabolic psychiatrists like those at Harvard and metabolic psychiatrists at Stanford. They're doing work in this field and understanding the connection between the brain and some of these systemic processes. Yeah, absolutely. And when you take a schizophrenic and you look at them with a PET scan, the positive emission tomography, what you'll see is their brain lights up. And that's because their microglia, which is their immune cells in the brain are on literally on fire. And unless you actually treat that, uh, the, a schizophrenic is at high risk for developing dementia down the

Starting point is 00:24:15 road because their fire is not being put out. And this Mark is, I'm going to mention this because when I was, I actually do, uh, I've, I've done, uh, some lectures, uh, for some lectures for American Academy of Anti-Aging Medicine on neuroinflammation. And in the process of preparing for that, I came up against some really fascinating things. One is that when you look at the genetics of schizophrenia, they did this whole genome-wide association studies of saying, well, what gene or what genes are associated with schizophrenia. And they did what's called a Manhattan plot. And on chromosome six, it sort of stood out like the Empire State Building. And what they found out is that on

Starting point is 00:24:59 chromosome six, chromosome six is highly involved with the immune system. So that tells us that a lot of patients who have schizophrenia have an issue on chromosome six related highly involved with the immune system. So that tells us that a lot of patients who have schizophrenia have an issue on chromosome six related to the immune system. And what I'm going to tell you next is absolutely positively fascinating. And this sort of blew me away. There were two case reports. And remember, case reports are just like a doctor observing, okay, this is interesting. Look what happened. You know, why did this happen? And the two case reports were this, and this tells you, you know, how the immune system is intimately involved in schizophrenia. One is a patient had refractory schizophrenia and developed some type of cancer and needed a bone marrow transplant.

Starting point is 00:25:42 The refractory patient with schizophrenia got a bone marrow transplant. A bone marrow transplant is basically giving you a new immune system. After he got the bone marrow transplant, guess what happened to his refractory schizophrenia? It was gone. What happened? Gone. Wow. It completely cleared up because it changed his immune response to whatever it was responding to.

Starting point is 00:26:02 I don't know. But his refractory schizophrenia went away. On the flip side, there was another gentleman who also needed a bone marrow transplant. He got his bone marrow from his brother who had schizophrenia. Guess what happened to him? He caught schizophrenia. Wow. That's pretty amazing. That's pretty amazing. Yeah. It is amazing. I was blown away by that. And I think that people who are doing, I'm a clinician, I'm seeing patients, but those case reports are really, really seminal to change how we think about how we see these conditions. And the fact that that can happen in the same way. I also found it fascinating that, you know,

Starting point is 00:26:45 we talk about the gut microbiome and how that's so important related to the immune system is that when you do stool transplants, you can literally transplant or infect a person and make them skinny, or you can transplant stool and make them fat. We can go both ways. They're doing this with autism and Parkinson's, right? They're actually doing fecal transplants with autism and with Parkinson's and seeing real changes in the brain function. That blows my mind when you think about that.

Starting point is 00:27:13 It does blow my mind. And the thing about this is we are still in the nascent period of really understanding this because it's not like, you know, you take this one chemical or you take this one probiotic and everything's fixed. It's a very, you know, you take this one chemical or you take this one probiotic and everything's fixed. It's a very, very complex array. And, you know, we have hundreds of different microbes and bacteria and viruses in the gut. So it's going to take us a while to figure this all out. But, you know, I think we're also in a very good stage where, you know, we have, you know, massive computing power and we have artificial intelligence. And I think that we're going to probably approach these areas of understanding neuroinflammation, and really

Starting point is 00:27:51 difficult to treat conditions like ALS, like schizophrenia, like Parkinson's and such. And we're going to be able to biohack them. And Alzheimer's, right, Alzheimer's. That's another thing, though, this is, you're bringing up one of my favorite things. So for years, Mark, what did neurology focus on with Alzheimer's? It was what? It was amyloid plaque, right? Amyloid plaque, all you got to do is get rid of the amyloid and you get rid of Alzheimer's. That's right.

Starting point is 00:28:18 So you get rid of cholesterol and you get rid of heart disease. Right. So guess what? The plaque, the beta amyloid plaque that was found in the brain, guess what that actually is? That's an antimicrobial peptide. The brain is producing beta amyloid in response to some type of organism, be it a virus, a bacteria, or a fungus. So when we see that, those are the footprints of a organism that the body is trying to attack. Yeah, absolutely. And I think, you know, we actually probably should have Rudy Tanzi on the podcast. He's a scientist at Harvard who specializes in Alzheimer's, and he has discovered the microbiome of the brain. So literally there are viruses, yeast, bacteria in the brain,

Starting point is 00:29:08 which we thought was sterile, that may be triggering this cascade of inflammation. And then the question is, where does this come from? And it seems like a lot of it may come from the gut, which is crazy. How does it get from your gut to your brain? But it does, and it triggers this neuroinflammation that's driving things like Alzheimer's. You know, I think, I think we often get stuck on one thing though,

Starting point is 00:29:29 right? In medicine, we stuck, it's stuck on it's this or it's that. And I think the important thing people remember is whatever your diagnosis is, it doesn't immediately tell you what the cause is. So you could have 10 people with Alzheimer's, they could have 10 different causes. And in one person, you could have three or four or five different causes, right? And I just remember one patient I had who was seven years old, really pretty significant. You know, Alzheimer's, not bedridden at this point, but pretty non-functional, also depression, and was struggling really badly. He was former CEO of his company, a family-run business, couldn't function anymore. Behavior was changing. His kids, grandkids, family didn't want to hang out with him anymore because he was acting inappropriate. And it turned out

Starting point is 00:30:11 he had so many things going on. I mean, the biggest thing he had was high mercury, which he lived in Pittsburgh and had exposed to all the steel plants. And they used coal ash for fertilizing land, and they put it on the streets in the winter instead of sort of salt for the icy roads. And he also had a mouthful of fillings. And he also had a terrible history of irritable bowel for 30 years. It was on stelazine, which is just like an antipsychotic. So it's like a relaxant for your gut, which is terrible.

Starting point is 00:30:39 But he had terrible gut issues and bacterial overgrowth and leaky gut and gluten sensitivity. And he also had insulin resistance. He had prediabetes. So essentially he had all these problems, heavy metals, microbiome issues, and he had insulin resistance or prediabetes, which we know drives inflammation in the brain. They're calling Alzheimer's often type 3 diabetes. And he had all these other biochemical issues

Starting point is 00:31:05 genetically like methylation problems and and which are the b vitamins we're also driving inflammation his brain because he wasn't able to produce antioxidants and glutathione and when we started to address all these things we got the mercury out we fixed his gut we cleaned up his diet we got rid of the sugar and starch. We optimized his B vitamins. He literally came back from the dead like Rip Van Winkle and was able to function, go back to work, be a functioning member of his family again. This is someone who would have just been said, okay, you have Alzheimer's and you are going to be in a nursing home and that's the end of that. And it was pretty miraculous to see that. It sort of woke me up to how by really being diligent with these patients, you can really help them either completely recover

Starting point is 00:31:45 or dramatically recover. And I've seen, you know, the spectrum from, you know, the tough cases of autism, Alzheimer's, you know, it depends how much they've got going on, how far down the road they are, but you see amazing stuff. But things like depression, bipolar disease, you know, mood disorders, it's often remarkable how quickly the brain responds, ADD. And it's something that we just, you know, unfortunately are not thinking about that well, ADD. And it's something that we just, you know, unfortunately are not thinking about that well in traditional medicine. And that's really why we do what we do with the Ultra Wellness Center. And we've treated nearly thousands and thousands of patients in this way. And we now do stuff virtually too, which is kind of fun. So we can see people from all over.

Starting point is 00:32:19 And we have a great team of physicians and nutritionists and practitioners who really help guide people through this space. Because, you know, what kills me, Todd, and I'm sure it kills you, is you hear story after story. And I'm sure you get this all the time. Hey, could you help this one? Could you help that one? Or my mom or my dad or my sister or my friend. And people are just struggling to find answers.

Starting point is 00:32:39 And, you know, when you hear the story, you go, oh, God, I know what's wrong with this person. But it's because we have a certain set of filters or lenses that we look at. And it's so gratifying. Can you think of any other cases that you want to share that sort of illustrate this? Yeah. I mean, I think I'd mentioned this. This is a, this is a fascinating case. I really can't, I can't a hundred percent prove it, but I talked about it when we talked about the oral systemic health connection is the connection with the mouth. And there's some really good evidence of the particular bacterium, which is a bad actor, and it's called Porphyromonous gingivalis. And I've seen this in a number of patients who have had early Alzheimer type symptoms. You can also see this oral bacteria in patients with rheumatoid arthritis.

Starting point is 00:33:26 So looking for this with DNA of the mouth organisms. And again, you know, this is to me is a really fascinating thing. You know, somebody says, well, Alzheimer's runs in our family. Well, poor Fremontis gingivalis may run in your family. You may be spreading the bacteria from person to person. And this bacteria, which is found in saliva, it stimulates the immune system in genetically susceptible individuals and can really lead to profound neuroinflammation. And in one patient in particular who I saw, he had Lewy body dementia, which is another form of inflammation. Lewy bodies, because on anatomical examination of the brain, they find these little things and they call them Lewy bodies, right?

Starting point is 00:34:11 It doesn't mean that they understand it. It's just Lewy found it and that's why they named Lewy body after Lewy. And that's actually what Robin Williams had. Robin Williams had Lewy body dementia with Parkinson's. So we call it Parkinson's. We put it in this neat little category, and then we call it Alzheimer's, or we call it dementia, and we put it in this little category, and then we call it Lewy body. And they're all sort of this interacting, overlapping kinds of things. And yeah, they can have different clinical presentations, but as you said, there can be many, many

Starting point is 00:34:41 factors that go into the origin of this neuroinflammatory process. And diet plays a huge role. You know, if you don't have the right nutrients, you don't have the right fatty acids, you're going to be more prone to all of your cellular membranes have omega-3 fatty acids. If you're not able to make the compounds in the body, which are called pro-resolving mediators or SPMs. And actually have this as a supplement now. These are actually quite fascinating compounds. The SPMs are a selective pro-resolving mediator compounds. They're basically turbocharged fish oil. And certain people, some people can't take their omega-3 fatty acids and turn them into these compounds.

Starting point is 00:35:28 And clinically, I have found them, they either work really well or they don't work. I don't know about you, Mark, but these are other things that you can use as a nutraceutical to help turn off inflammation in someone who's got some chronic inflammation. Not to say if you take it, it's going to help with Alzheimer's per se, but it's one of the other tools that we can use to modulate the inflammatory response in the body. Yeah, so true. You know, we often in traditional medicine don't know how to evaluate the brain properly because we're just looking at the brain, but we have to look systemically. And that's really what we do in functional medicine. And, you know, Dale Bredesen coined the term a cognoscopy, like a colonoscopy, but for your brain. And it's looking at all the things we've been talking about, looking at diet, looking at nutrient levels, looking at hormones, looking at toxins, at the microbiome in the gut, looking at infections, looking at mold, looking at allergens, looking at the overall health of the person and seeing what of those things are driving adverse consequences for

Starting point is 00:36:26 the brain and for brain function. And any individual, the same cause might cause different things. So one person might cause schizophrenia, another person might cause Alzheimer's, then the person might cause depression. So we really have the tools to look at a true cognoscopy. And then the question is, how do we help help the brain repair how do we set up the conditions for the brain repair so let's talk about how from a traditional functional medicine point of view we actually treat these people because it's a pretty systematic approach that addresses diet and lifestyle and also some of these underlying causes yeah i mean so we as you mentioned mark we do a lot of the testing so we'll do organic acid testing, which is checking for the nutrient metabolites that are found in the body.

Starting point is 00:37:07 We'll also do gut microbiome testing, looking at all of the different bacteria, viruses, yeast, parasites potentially in the body. We'll look at markers for leaky gut. The other test that I do is a leaky brain. You know, just like you can have leaky gut, you can have a leaky brain. There's actually a test for that. Cyrex Laboratories does the does the blood brain barrier test. You can check also for neuro autoimmune markers with the Cyrex 7X test. Again, you can do gut microbiome testing. The one that I like to use is the GI map test because I think it's,

Starting point is 00:37:41 it's quantitative PCR. So I find it to be very helpful. I think the whole GI realm area is an area that we're just learning. And there's going to, I think as time goes on, these tests are going to get better and better. But I find that to be very, very helpful to distinguish what's going on inside the person that I have. The other thing, which I think is also really, really critical, Mark, is sleep. And this is something that I have. The other thing, which I think is also really, really critical, Mark, is sleep. And this is something that I really emphasize to people, is that when our bodies sleep, our brains take out the garbage. Okay. And I'll guarantee you, when you have a patient who's got a neurodegenerative condition, one of the first things that you'll see is disruptions of their sleep. And what happens is during the day, you know, our brain only comprises 2% of our body weight, but it uses

Starting point is 00:38:33 20% of our body's energy, which means that there's a lot of metabolic activity. And what happens throughout the day is we get metabolic waste products that build up in the brain and our brain flushes them out during deep delta sleep. If we don't get that deep sleep, we can't flush the brain and take the garbage out in the brain. And those toxins build up, those things that metabolic byproducts, misfolded proteins, inflammatory molecules, amyloid, et cetera, build up in the brain and can affect how the person's cognition is, their memory, their mood, et cetera. It's amazing. Yeah. And I think the diet is such a huge role too in the brain. I mean, we see that the diet we're eating is a highly inflammatory diet in this country of processed foods, inflammation that are driven by sugar and starch, excess refined oils, all the lack of things that are anti-inflammatory, the whole

Starting point is 00:39:35 foods with all the phytochemicals in them and the nutrient-dense foods. So we're eating a diet that's super inflammatory. So this is the first thing. And often dairy and gluten are among the worst. And then we focus on how do we get the right nutrients? Because if you're low in certain nutrients, whether it's the antioxidant nutrients or the B vitamins, your body needs these nutrients to regulate your immune system to function, whether it's zinc or vitamin A or selenium or vitamin D, vitamin C, all these are really necessary for proper regulation of the immune function. So getting adequate levels of these is key. Also, we really get people on an elimination diet if we suspect or we test that they have sensitivity to certain foods. We treat the underlying infections if we

Starting point is 00:40:14 find them directly with antibiotics if we need to, antivirals, or sometimes we'll use herbal therapies or things like ozone and other approaches to deal with infections. We'll fix the gut. Often that's a big issue. So we have a whole functional medicine approach to deal with infections. We'll fix the gut. Often, that's a big issue. So we have a whole functional medicine approach to fixing the gut. We've talked about a lot on this podcast. And then we'll address whatever toxins that are there and help you eliminate the toxins through a really focused detoxification program. And so building on the framework of functional medicine, we can identify in each individual which of these things are the problem. And then we can start to map the right treatments for that person. And it's so gratifying when you see this in people's lifelong depression gets better. I mean,

Starting point is 00:40:52 there was a woman who was severely depressed, who was in and out of psychiatric hospitals, on lots of medications. Her marriage was falling apart. She wasn't able to really work at work anymore. She was about to get fired from her job. Very overweight, diet, obviously high in sugar, starch, and processed foods. And she did the Daniel Plan, which is a faith-based wellness program, but it's based on a whole foods, anti-inflammatory, pegan-ish diet, essentially. And she said at the six-week reunion, she's like, Dr. Hyman, after three days of changing my diet, my depression went away. And I've been on piles of medications, in and out of hospitals, admitted for severe depression to hospitals many times in my life, and it's just gone. And I'm like,

Starting point is 00:41:34 she goes, is that possible? I'm like, yeah, it's possible. If whatever you're eating was triggering the inflammation in your brain, you stopped it, yes. So it's really a sort of untapped reservoir of tools and tests and therapies that traditional medicine, psychiatry, neurology are just not using and is really where the money is. And you bring up a really good point, Mark, because I often ask my patients who are seeing a psychiatrist, and I'm not going to bash psychiatrists, but I think the profession of psychiatry is in the dark ages. I can't remember the last time a psychiatrist that I've seen has done a blood test or examined the patient. And I think that a lot of psychiatrists would actually do a good job if they actually took a psych course in neurology to really understand how the brain is working. So if you're a psychiatrist and you're seeing a patient and you are not utilizing a good nutritionist, preferably a functional medicine nutritionist, if you're not doing some blood testing and you're not actually examining your patient, you may be doing more harm than good. And the other pet peeve about the psychiatric world is that we are now medicating young children in ways that are unexplored. We're

Starting point is 00:42:47 doing polypharmacy in the young, polypharmacy in the old with these neuropsych drugs that are advertised on television. And it is a complete, if you will, show. Excuse my French. It is awful. It's a terrible thing in this country. And I'll stand up here and I'll shout from the rooftops because this is a bad thing that we're doing to the brains of our people, the brains of our young kids. This is something that we should not be doing, period. No, I mean, it's true. We really are relying on downstream treatment. So when the neurotransmitters go awry, whether it's depression or autism or Alzheimer's or ADD, you know, we go, well, how do we fix the neurotransmitters? And the question isn't how do we fix the neurotransmitters? The question is, why are the neurotransmitters so screwed up in the first place? And it's because

Starting point is 00:43:36 of these phenomena. And one of the great examples I'll see is that the basic driver of inflammation is diet, but there are other factors. And anything that causes inflammation can interfere with our enzyme function and throughout our bodies. And there's a key step in converting serotonin, I mean, tryptophan into 5-hydroxy tryptophan into serotonin, which is the happy mood chemical. And when you get a high-level inflammation in the body, that enzyme is sort of blocked, and you end up with this byproduct called kynuret, I don't know if I'm pronouncing it right. I almost read it. I don't know what I said. Kynuretic acid, right. Yeah, kynuretic acid. And that level goes up, and you can actually measure it in these patients.

Starting point is 00:44:27 And you see when they have high levels of these quinolinate or kynurenic acid, it indicates inflammation. And you know that the serotonin pathway is being screwed up, and it's bypassing and producing these toxic molecules that cause inflammation in the brain. And so one, by getting rid of the inflammation, two, by giving the helpers for these chemical reactions, you can often really help improve the cognitive function of the brain. But it's really about the inflammation. And that's what's so different and striking about it. You know, it's interesting you say that, Mark, because I used to lecture for a metametrics laboratory who does the organic acid testing. I'll never forget when I first learned about the quinolinic acid and that quinolinic acid is measured the organic acid testing, I'll never forget when I first learned about the quinolinic acid and that quinolinic acid is measured on organic acid testing. And this compound was

Starting point is 00:45:12 actually first isolated in patients who had AIDS dementia. And what they found is that, as you mentioned, how that pathway gets switched over, various things like viruses, like the AIDS virus can actually upregulate the production of quinolinic acid. And high levels of quinolinic acid cause the brain to become inflamed. They cause the brain to shrink and they can potentially cause Alzheimer's or dementia type symptoms. And that's where AIDS dementia was basically how we found the importance of quinolinic acid. I'll bet you there's not many psychiatrists who are measuring quinolinic acid in their psych patients or even neurologists who are doing that. Yeah, we do. At the Ultra Wellness Center, we definitely do. And we see so much from that data

Starting point is 00:46:01 that can help us figure out how to help these patients. And that's, that's really what's to me. So, so exciting. Well, you know, I also, this is, this is, I'm going to go back to when I went through my training, cause I went, I trained at Dartmouth and I went to a great education at Dartmouth medical school. And one of my neurology professors was Dr. Alex Reeves, and he was a fantastic teacher and wonderful, open-minded, energetic, enthusiastic guy. And he really helped me to understand how the brain works and also understand how it's connected to the mood and your whole being. And I also had, when I did my psychiatric training at Dartmouth, I had another mentor who was board certified both in psychiatry and neurology.

Starting point is 00:46:48 So that's where I really got, and he was someone who would actually order tests on patients and understand that, you know, let's try to figure out what's going on. This was, you know, way before functional medicine was prominent. And it got my own brain thinking about, you know, neuropsychiatry and, and, and it's a fascinating field is there's, you can't split them. Neurology and psychiatry are one. And when you, when you think that they're, that they're separate, are you, you know, you have this dichotomy and you're just, you're not going to, you're not going to help neurological patients and you're not going to help the psych patients. You need to think in neuropsychiatrically. Well, I'm sure this happened to you like it happened to me.

Starting point is 00:47:28 But, you know, I started practicing functional medicine. I wasn't focused on the brain. I wasn't focused on, you know, treating people by dealing with the, you know, the things that I thought were focused on the brain. I was really focused on fixing their health issues. People came in with irritable bowel or they came in with asthma or came in with irritable bowel, or they came in with asthma, or they came in with an autoimmune disease, or they came in with whatever they came in with. And I would literally work on that problem. So fix their gut or fix their, their whatever is going on. And incidentally, their psychiatric problems would get better, or their their ADD would get better. And they would report, Dr. Hyman, I'm not depressed anymore. My panic attacks are gone. My OCD is better. You know,

Starting point is 00:48:09 my memory is better. I was like, well, what's going on here? And so I began to go, wait a minute. And I didn't really come at this from an academic point of view. I came at it from a clinical point of view. And I started noticing if you pay attention to your patients, like listen to them, they'll actually tell you what's going on. I'm like, well, something's going on here. And that's really what led me to write the book, The Ultra Mind Solution, which is how to fix your broken brain by fixing your body first. And that book is a little dated now, but honestly, if I look back at it, I think it's still way ahead of its time even now, because it's talking about the ideas that were, you know, then were in the

Starting point is 00:48:42 literature, but just really beginning and stuff that I saw clinically, like the role of, for example, tick infections, the role of the gut microbiome. I mean, who's talking about the microbiome in the brain 15 years ago? Nobody. But we were paying attention to this and we saw these patients get better. And I was like, wow, this is a whole new field. So that's really why I wrote that book. And I can't tell you how many people have said to me, I got that book and it changed my life. I followed the directions. It's basically a step-by-step guide on how to fix your own brain. And sometimes you need help with doctor. And there's even sections in there and what to do if you need to go see a doctor and what tests you should ask for. But it's, it's really was striking to me. And I remember this one patient came in after a while, after I'd written the book about a year later and I said, Oh, why

Starting point is 00:49:19 are you here? So, well, you know, I'm pretty good. I'm like, well, what's going on? Well, you know, a while ago I had all these brain issues and depression and memory issues and blah, blah, blah, blah. And I'm like, well, why are you here then if you're better now? She says, well, I read your book and I followed all the directions and I got better. It took nine months to get an appointment. And I said, maybe you can help me get even better. I'm like, okay. So what was so beautiful about it was that I literally took the science of what we do in functional medicine and applied it into practical steps for people to do. And sometimes people need to dig deeper. But I think it's such a gratifying field that we're in, Todd, because we get to see how people really can transform by fixing the root causes, by looking at the underlying biology, by treating the system, not the symptoms, by helping deal with this brain on fire through looking at all the factors that can interfere with it. So again, everybody listening, you've been listening

Starting point is 00:50:09 to podcasts at Doctors Pharmacy, House Call. We've been talking about brain on fire, neuroinflammation. It's linked to every known psychiatric and neurologic disease. So if there's anything wrong with your brain, you better look at the inflammation that's causing it. And if you love this podcast, please share with your friends and family on social media. Maybe they would benefit from hearing about the brain on fire. Leave a comment of how you've dealt with your brain. I'd love to know more about your struggles and successes and subscribe wherever you get your podcasts. And we'll see you next time on The Doctor's Pharmacy. Hey everybody, it's Dr. Hyman. Thanks for tuning into The Doctor's Pharmacy. I hope you're loving this podcast. It's one of my favorite things to do and introducing you all the experts that I know

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The Dr. Hyman Show - Is Brain Inflammation The Cause of Depression, Dementia, ADD, And Autism? A Functional Medicine Approach To Neuroinflammation with Dr. Todd LePine

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