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Episode 57
The Doctor's Farmacy: House Call

Is Brain Inflammation The Cause of Depression, Dementia, ADD, And Autism? A Functional Medicine Approach To Neuroinflammation

Open the Podcasts app and search for The Doctor’s Farmacy. If you’re viewing this site on your phone, you can just tap on the

Tap the subscribe button and new shows will be added to your library.

If you’re using a different device, our show is available on the following platforms.

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The emphasis on naming diseases is pervasive throughout medicine, and it is a primary obstacle to changing the way we do things and finding answers to our health problems. For instance, two brain disorders with two completely different names might have a lot more in common than you may otherwise think. The brain has an incredible connection to the immune system, called the glymphatic system, which helps it detoxify, receive valuable nutrients, and more. When the glymphatic system is threatened, neuroinflammation is created.

In this episode, Dr. Hyman speaks with Dr. Todd LePine about inflammation in the brain. They discuss the many factors that can drive neuroinflammation, the range of conditions that are linked to brain inflammation, and how they work with patients to cool this inflammation.

Dr. LePine graduated from Dartmouth Medical School and is Board Certified in Internal Medicine, specializing in Integrative Functional Medicine. He is an Institute for Functional Medicine Certified Practitioner. Prior to joining The UltraWellness Center, he worked as a physician at Canyon Ranch in Lenox, MA, for 10 years. Dr. LePine’s focus at The UltraWellness Center is to help his patients achieve optimal health and vitality by restoring the natural balance to both the mind and the body. His areas of interest include optimal aging, bio-detoxification, functional gastrointestinal health, systemic inflammation, autoimmune disorders, and the neurobiology of mood and cognitive disorders. Dr. LePine teaches around the world, and has given lectures to doctors and patients at American College for Advancement in Medicine (ACAM), Age Management Medicine Group (AMMG), the University of Miami Integrative Medicine Conference, The Kripalu Center in Lenox, MA, and is on the faculty for American Academy of Anti-Aging Medicine (A4M). Dr. LePine is the head of the Scientific Advisory Board for Designs for Health and a consultant for Diagnostic Solutions Laboratory. He enjoys skiing, kayaking, hiking, camping, and golfing in the beautiful Berkshires, and is a fitness enthusiast.

This episode is sponsored by Thrive Market and Athletic Greens.

Thrive Market is offering all Doctor’s Farmacy listeners an extra 25% off your first purchase and a free gift when you sign up for Thrive Market. Just head over to thrivemarket.com/Hyman.

Athletic Greens is offering Doctor’s Farmacy listeners a full year supply of their Vitamin D3/K2 Liquid Formula free with your first purchase, plus 5 free travel packs. Just go to athleticgreens.com/hyman to take advantage of this great offer.

In this episode, Dr. Hyman and Dr. LePine discuss:

  • Glial cells, microglial cells, and dark matter of the brain
  • How conditions such as Alzheimer’s disease, ALS, multiple sclerosis, schizophrenia, depression, strep infection, PANDAS, and more are related to neuroinflammation
  • Drivers of inflammation in the body and brain, including stealth infections
  • Parkinson’s disease and gut health
  • Patient cases that Dr. Hyman and Dr. LePine have treated
  • The genetics of schizophrenia
  • The microbiome of the brain
  • The oral-systemic health connection
  • The Functional Medicine approach to repairing the brain
  • Why diet and sleep are key to brain health

I hope you enjoyed this conversation as much as I did. Wishing you health and happiness,
Mark Hyman, MD
Mark Hyman, MD

Guest

 
Mark Hyman, MD

Mark Hyman, MD is the Founder and Director of The UltraWellness Center, the Head of Strategy and Innovation of Cleveland Clinic's Center for Functional Medicine, and a 13-time New York Times Bestselling author.

If you are looking for personalized medical support, we highly recommend contacting Dr. Hyman’s UltraWellness Center in Lenox, Massachusetts today.

 
Dr. Todd LePine

Dr. LePine graduated from Dartmouth Medical School and is Board Certified in Internal Medicine, specializing in Integrative Functional Medicine, and is an Institute for Functional Medicine Certified Practitioner.  He has been practicing Functional Medicine for over 15 years focusing on Optimal Aging, Bio-Detoxification, Gastrointestinal Health, Systemic Inflammation, Autoimmune disorders and the Neurobiology of mood and cognitive disorders.

Show Notes

  1. Is Alzheimer’s Reversible? Getting to the Root Causes
  2. The Science Of Mood And Your Microbiome
  3. How To Recover From Chronic Lyme And Tick Diseases with Dr. Todd LePine
  4. The Functional Medicine Approach To Oral Health with Dr. Todd LePine
  5. Hack Your Sleep

Transcript

Dr. Todd Lepine:
Depression is not about serotonin. Yes, serotonin is an important neurotransmitter, but a large part of depression is actually related to neuroinflammation.

Dr. Mark Hyman:
Welcome to Doctor’s Farmacy. I’m Dr. Mark Hyman and that’s Farmacy with an F, a place for conversations that matter. And 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. And 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 Farmacy with Todd Lepine, again, one of my great docs from the UltraWellness Center. We’ve been working together for gosh, almost 30 years now. And we see so much of this, Todd.

Dr. Mark Hyman:
Todd is a graduate from Dartmouth. He’s an incredible physician. 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.

Dr. Todd Lepine:
Well, thanks Mark. I’m excited to be talking this afternoon.

Dr. Mark Hyman:
Okay. 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 from Dr. Perlmutter who is a neurologist, which is that most brain diseases are diseases of brain inflammation. But when the brain is inflamed, it doesn’t 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. Talk about how we think about the brain and how Traditional Medicine thinks about the brain in terms of, of how we approach the issue of inflammation.

Dr. Todd Lepine:
Well, you could 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 nerves talk to each other and there’s millions of them and it was all about understanding that and neurotransmitters, epinephrine and serotonin and dopamine. But what we are 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. In physics we know about dark matter. Most of the universe is actually dark matter. We don’t, we can’t really see it and it’s not there.

Dr. Todd Lepine:
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.

Dr. Mark Hyman:
Yeah.

Dr. Todd Lepine:
Glial cells actually come from the Latin term meaning glue. It’s the cells that hold the brain together. Only about 10%o 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.

Dr. Todd Lepine:
And neuroinflammation is incredibly important. A lot of the things that we see in our day to day practice, you mentioned it. Depression. Depression is not about serotonin. Yes, 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, 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. It’s really 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.

Dr. Todd Lepine:
And then there’s the other thing. I don’t see children, but PANDAS. I’m sure you have probably cases of patients-

Dr. Mark Hyman:
Yes.

Dr. Todd Lepine:
… who have PANDAS, which is the pediatric autoimmune neuropsychiatric disorders related to strep infections.

Dr. Mark Hyman:
Yeah.

Dr. Todd Lepine:
And this can be a devastating clinical scenario where all of a sudden this young boy or girl starts getting these strange neurological type behaviors, these tics, these OCD type behaviors, etc. And these things are driven by neuroinflammation. The original description was that it was due to a strep infection. Mothers and fathers know about that because when their kid gets a sore throat, they take them to the doctor and 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 glomerular nephritis. 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 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.

Dr. Mark Hyman:
Yeah. It’s just such a remarkable 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 mention the glial cells which is the brain’s immune system that cleans things up, but there’s so many things that screw it up and including lack of sleep which is a big one. That’s when it’s really active. But I know I’ve seen-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… in my practice that focusing on brain inflammation has led to the most miraculous cures for all sorts of “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 in my mind, he hasn’t even been thought of having PANDAS, but he might have a low-grade inflammation response from the strep that’s been going on for 30 or 40 years, but nobody picked it up.

Dr. Mark Hyman:
We see all of this kind of stuff, whether it’s depression… And depression, we think “Oh, but that’s a mood disorder. Well yeah, it is a mood disorder but sometimes it’s because you have a loss or some tragedy in your life and gee that’s [inaudible 00:07:30] temporary, but these chronic mood disorders are often related to brain inflammation and they’ve even talked about using drugs for rheumatoid arthritis for depression to shut off the inflammation of the brain. And I think that’s a bad idea, but what’s causing all this brain inflammation-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… that’s leading to this rampant epidemic of brain diseases? I wrote a lot about this in The UltraMind Solution over a decade ago and it’s only increased in terms of the prevalence of these problems and the data linking inflammation and actually uncovering some of the causes of inflammation that are driving this.

Dr. Mark Hyman:
And can you tell me about-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… what… From a traditional perspective, what we do is we give you medications, we give you antidepressants and we’re not actually giving anti-inflammatories for Alzheimer’s although they tried giving people Advil and see what happens, but it didn’t work. What is a approach we take to finding out what the causes are?

Dr. Todd Lepine:
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 Medicine is we have the time and we take the time to actually listen. And listen to the patient’s story.

Dr. Todd Lepine:
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. It’s really about mapping out the timeline of when did the patient’s symptoms start? How old were they? What was happened 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? There’s all different kinds of things that can trigger inflammation and that’s where you really have to play medical detective. And sometimes you’re going to find it on the first time. Sometimes you’re not. It might take you a lot of uncovering, lifting up stones, leaving no stone unturned.

Dr. Todd Lepine:
And that’s where a Functional Medicine approach where we do a lot of advanced testing to look for 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.

Dr. Mark Hyman:
Yeah.

Dr. Todd Lepine:
It’s a real… You have to play detective is the key.

Dr. Mark Hyman:
It is. And the key things that really drive the problems are the usual things we see that drive inflammation in general, whether it’s autoimmune disease or anything else. It’s toxins, it could be all the environmental toxins. We see this in Parkinson’s. The 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 [inaudible 00:10:36] for The Doctor’s Farmacy 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. 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 this as a force to be reckoned with in terms of the brain.

Dr. Mark Hyman:
And so we have to understand the-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… microbiome’s role, toxins, foods. For example, gluten can be very inflammation for the brain for many, many people because it produces both inflammation 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 inflame the brain. And then, of course, there are infections that you were talking about like viruses or tick infections and so forth. These all can be driving brain inflammation.

Dr. Mark Hyman:
In Functional Medicine what we do is we go “Wait a minute, well 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 Medicine is we have a set of tools and a set of therapies that allow us to 1) identify the causes and 2) to actually treat them directly. And it’s pretty exciting because we do see a lot of changes-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… from people’s health.

Dr. Todd Lepine:
Absolutely. And you were talking about the connection with the gut and there’s really some fascinating stuff. When I was in training, we talked about Parkinson’s. And Parkinson’s is the old, old person’s disease. 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 spectrum illness and there is a big connection between patient 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.

Dr. Todd Lepine:
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 and the yeast actually do a metabolism of those foods and will produce these chemicals which are called the metabolome or the gut micrometabolome. And those metabolites in some people can affect the brain. And in essence, you sniff out Parkinson’s. And she actually did that. She actually could, she sensed that there was 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.

Dr. Mark Hyman:
Dogs can tell my 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.

Dr. Todd Lepine:
I prescribe-

Dr. Mark Hyman:
[crosstalk 00:13:33]

Dr. Todd Lepine:
… dogs all the time.

Dr. Mark Hyman:
It’s like-

Dr. Todd Lepine:
It’s one of my, it’s on my prescription pad. Absolutely. Yeah.

Dr. Mark Hyman:
It’s interesting. The body knows. And I think maybe we can just share as a way of illustrating the power of addressing inflammation on the brain with some cases. I have a bunch of cases from autism to Alzheimer’s, but it would be good to get a sense from your experience. What are the things that show up and how did you treat it and what happened?

Dr. Todd Lepine:
Well, I’ve had a whole variety of cases. In fact, a couple of cases that we’ve had at a clinic where we had some patients who presented to psychiatric hospitals. And when it came out, 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 had a couple of recent cases where the patient’s underlying trigger was Lyme disease which is a condition.

Dr. Todd Lepine:
And 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 a condition which was readily treated and it’s pretty much gone although there is still some recurrences of it. But syphilis 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.

Dr. Mark Hyman:
Yeah.

Dr. Todd Lepine:
That’s one of the conditions that can trigger neuroinflammation. And then also there was a recent case of Bartonella, also causing neuropsychiatric conditions and a “diagnosis” of schizophrenia. It’s really a fascinating field. And the problem is that psychiatrists are not trained to think this way. And neurologists are not trained to step over into psychiatry. They’re two different fields, but they’re really the same field. So it’s neuropsychiatry. This is the area that is actually really quite fascinating to me. People always ask me “What kind of doctor are you?” And I have my own description-

Dr. Mark Hyman:
Yeah, I can answer that question.

Dr. Todd Lepine:
Yeah. I’m a psychoneuroimmunoendogutologist. And basically-

Dr. Mark Hyman:
There you go.

Dr. Todd Lepine:
… looking at the whole connection between the brain, the guy, the immune system and all of the body when it’s all interconnected. And it’s really, really fascinating and you can really help these people who are having significant conditions.

Dr. Mark Hyman:
So what happened? You saw this patient with schizophrenia, right? And you found the tick infections. What happened then?

Dr. Todd Lepine:
We were able to get their symptoms down by treating the underlying cause which is the underlying spirochetal infection. I also have 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. It’s a really fascinating thing.

Dr. Todd Lepine:
And one of the tests that you can do that can check for this, it’s not a common test and 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 something that any doctor who has a patient who has gone “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.

Dr. Mark Hyman:
Yeah. It’s quite incredible. And I’ve had patients who had schizophrenia before or bipolar disease and you think these problems are just so intractable. And so difficult to treat.

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
And they can be. But in fact, the whole field of Functional Medicine came out of the field of psychiatry with Abram Hoffer’s discovery that you could treat schizophrenia using nutrients and helping to improve the biochemistry of the brain. And then Linus Pauling wrote his seminal paper Orthomolecular Psychiatry in 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-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… biochemistry. And that’s called orthomolecular which means to straighten. And that has really led to the whole field of Functional Medicine. And we then expanded on that with our understanding of the role of inflammation of the brain. And many schizophrenic patients have high levels of, for example, gluten antibodies. About 20% of schizophrenics have anti-gliaden antibodies in their bloodstream.

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
When you take the gluten away, they do better. That’s causes Brian 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.

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
When you start to think about that, it’s like, “Wait a minute. We are treating this completely incorrectly.” And this is what is classical Traditional Medicine, you treat the symptoms, not the cause. And Functional Medicine’s 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 toxin. Or it might be an infection. Or it might be mold. It might be all sorts of things that we are missing the boat on.

Dr. Mark Hyman:
And so we have this potential to rethink our whole approach to brain science. That’s why it’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 at Stanford. They’re doing work in this field of understanding the connection between the brain and some of these systemic processes.

Dr. Todd Lepine:
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 literally on fire. And unless you actually treat that, a schizophrenic is at high risk for developing dementia down the road because their fire is not being put out. And this, Mark, is… I’m going to mention this because when I was… I’ve done 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.

Dr. Todd Lepine:
One is that when we look at the genetics of schizophrenia, there’s this whole genome-wide association studies saying what genes are associated with schizophrenia. And they did what’s called a Manhattan plot. And on chromosome 6, it stood out like the Empire State Building. And what they found out is that on chromosome 6, chromosome 6 is highly involved with the immune system. That tells us that a lot of patients who have schizophrenia have an issue on chromosome 6 related to the immune system. And what I’m going to tell you next is absolutely positively fascinating and this blew me away.

Dr. Todd Lepine:
There were two case reports, and remember case reports are just a doctor observing “Okay, this is interesting. Look what happened. Why did this happen.” And the two case reports were this. And this tells you 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. The refractory patient with schizophrenia got a bone marrow transplant. Bone marrow transplant is basically giving a new immune system. After he got a bone marrow transplant, guess what happened to his refractory schizophrenia. It was gone.

Dr. Mark Hyman:
What happened?

Dr. Todd Lepine:
Gone.

Dr. Mark Hyman:
Wow.

Dr. Todd Lepine:
It completely cleared up because it changed his immune response to whatever it was responding to, I don’t know. But his refractory schizophrenia went away.

Dr. Todd Lepine:
On the flip side, there was another gentleman who also needed a bone marrow transplant. He got his bone marrow from his brother who has schizophrenia. Guess what happened to him? He caught-

Dr. Mark Hyman:
He got schizophrenia?

Dr. Todd Lepine:
… he caught schizophrenia.

Dr. Mark Hyman:
Wow.

Dr. Todd Lepine:
It goes both ways.

Dr. Mark Hyman:
That’s pretty amazing. That’s pretty amazing. Yeah. That’s pretty amazing.

Dr. Todd Lepine:
It is amazing. I was blown away by that and I think people who are doing… I’m a clinician. I’m seeing patients. 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-

Dr. Mark Hyman:
Hey, everybody, this is Dr. Hyman. Thanks for tuning into The Doctor’s Farmacy. I hope you’re loving this podcast. It’s one of my favorite things to do, introduce to you all the experts that I know and I love and that I’ve learned so much from. And I want to tell you about something else I’m doing which is called Mark’s Picks. It’s my weekly newsletter and in it I share my favorite stuff from foods to supplements to gadgets to tools to enhance your health. It’s all the cool stuff that I use and that my team uses to optimize and enhance our health. And I’d love you to sign up for the weekly newsletter. I’ll only send it to you once a week on Fridays. Nothing else, I promise. And all you do it go to drhyman.com/picks to sign up. That’s drhyman.com/picks P-I-C-K-S and sign up for the newsletter and I’ll share with you my favorite stuff that I use to enhance my health and get healthier and better and live younger longer. Now back to this week’s episode.

Dr. Todd Lepine:
I also found it fascinating that we talk about the gut microbiome and how that’s just 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-

Dr. Mark Hyman:
Right.

Dr. Todd Lepine:
… stool and make them fat. We can go both ways.

Dr. Mark Hyman:
[crosstalk 00:23:45] autism-

Dr. Todd Lepine:
And we don’t [crosstalk 00:23:47]

Dr. Mark Hyman:
… Parkinson’s, right? They’re actually doing fecal transplants-

Dr. Todd Lepine:
Yes.

Dr. Mark Hyman:
… for autism and with Parkinson’s and seeing real changes in-

Dr. Todd Lepine:
Exactly.

Dr. Mark Hyman:
… in the brain function. That blows my mind when you think about that.

Dr. Todd Lepine:
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 take this one chemical or you take this one probiotic and everything’s fixed. It’s a very, very complex array. And 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 I think we’re also in a very good stage where we have massive computing power. We have artificial intelligence and I think that we’re going to probably approach these areas of understanding neuroinflammation in really difficult to treat conditions like ALS, like schizophrenia, like Parkinson’s and such, and we’re going to be able to-

Dr. Mark Hyman:
Alzheimer’s.

Dr. Todd Lepine:
… biohack them. And Alzheimer’s. Right. Alzheimer’s. And that’s another thing. You’re bringing up one of my favorite things. For years, Mark, what did neurology focus on with Alzheimer’s? It was what, it was-

Dr. Mark Hyman:
Amyloid. Amyloid.

Dr. Todd Lepine:
Amyloid plaque. Right?

Dr. Mark Hyman:
Yeah.

Dr. Todd Lepine:
Amyloid plaque and all you got to do is get rid of the amyloid and you get rid of-

Dr. Mark Hyman:
Yeah.

Dr. Todd Lepine:
… Alzheimer’s. Right? You get rid of-

Dr. Mark Hyman:
I didn’t work out so well.

Dr. Todd Lepine:
… cholesterol and get rid of heart disease. Right.

Dr. Mark Hyman:
Yeah.

Dr. Todd Lepine:
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-

Dr. Mark Hyman:
Wow.

Dr. Todd Lepine:
… beta amyloid in response to some type of organism, be it a virus, a bacteria or a fungus. When we see that, those are the footprints of an organism that the body is trying to attack.

Dr. Mark Hyman:
Yeah. Absolutely. And I think I should probably have Rudy Tanzi on the podcast. He’s a scientist at Harvard who specializes-

Dr. Todd Lepine:
[crosstalk 00:25:43]

Dr. Mark Hyman:
… in Alzheimer’s. And he has discovered the microbiome-

Dr. Todd Lepine:
Yes.

Dr. Mark Hyman:
… of the brain. Literally there are-

Dr. Todd Lepine:
Yes. Yeah.

Dr. Mark Hyman:
… viruses, yeast, bacteria in the brain which we thought was sterile that may be triggering this cascade of inflammation and 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. And I think we often get stuck on one thing, though, right? In medicine. We get stuck on “It’s this,” or “It’s that.” And I think the important thing for people to remember is whatever your diagnosis is, it doesn’t immediately tell you what the cause is. You could have 10 people without Alzheimer’s, they can have 10 different causes. And in one person, you could have-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… three of four or five different causes, right? And I just remember one patient I had who was 70 years old, really pretty significant 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, family run business, couldn’t function anymore. His behavior was changing. His kids, grandkids, his family didn’t want to hang out with him anymore because he was acting inappropriate. And it turned out he had so many things going on. The biggest thing he had was high mercury-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… which he lived in Pittsburgh and had exposed to all the steel plants. And they use coal ash for fertilizing land and they put it on the streets in the winter instead 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 and was on Stelazine which is just like an antipsychotic so it’s like a relaxant for your gut which is terrible. But he had terrible gut issues and bacterial overgrowth and leaky gut and gluten sensitivity. And he also had insulin resistance. He had prediabetes. Essentially he had all these problems. Heavy metals, microbiome issues and he had insulin resistance or prediabetes which we know drives inflammation of the brain and they’re calling Alzheimer’s often type 3 diabetes. And he had all these other biochemical issues-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… genetically like methylation problems which are the B vitamins that were also driving inflammation in his brain because he wasn’t able to produce antioxidants and glutathione.

Dr. Mark Hyman:
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 [inaudible 00:28:10] and was able to function and go back to work.

Dr. Todd Lepine:
Wow.

Dr. Mark Hyman:
Be able to be a functioning member of his family again. This is someone who would’ve 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.

Dr. Todd Lepine:
Right.

Dr. Mark Hyman:
It woke me up to how, by really being diligent with these patients, you can really help them either completely recover or dramatically recover.

Dr. Mark Hyman:
And I’m seeing the spectrum from the tough cases of autism, Alzheimer’s, it depends on how much they’ve got going on and how far down the road they are, but you see amazing stuff. With things like depression, bipolar disease, mood disorders it’s often remarkable how quickly the brain responds. ADD. And it’s something that we just unfortunately are not thinking about that well in Traditional Medicine. And that’s really why we do what we do at the UltraWellness Center. We’ve treated literally thousands and thousands of patients in this way and we now do stuff virtually too, which is fun because we can see them from all over. And we have a great team of physicians and nutritionists and practitioners who really help guide people through this space.

Dr. Mark Hyman:
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, my friend?” And people are just struggling to find answers. And 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.

Dr. Mark Hyman:
Can you think of any other cases that you want to share that illustrate this?

Dr. Todd Lepine:
Yeah. I think I mentioned this. This is a fascinating case. And I really 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 Porphyromonas gingivalis. And I have 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. Looking for this with DNA of the mouth organisms.

Dr. Todd Lepine:
And again, this to me is a really fascinating thing. You know how somebody says “Well, Alzheimer’s runs in our family.” Well Porphyromonas 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. With Lewy Body on anatomical examination of the brain, they find these little things and they call them Lewy Bodies. Right. It doesn’t mean that they understand it. It’s just Lewy found it and they named it Lewy Body after Lewy. And that actually is what Robin Williams had. Robin Williams had Lewy Body dementia-

Dr. Mark Hyman:
Yes.

Dr. Todd Lepine:
… with Parkinson’s. 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 there were all this interacting overlapping kinds of things. And yeah, they can have different clinical presentations, but as you said, there can be many, many factors that go into the origin of this neuroinflammatory process.

Dr. Todd Lepine:
And diet plays a huge role. If you don’t have a right nutrients, you don’t have the right fatty acids, you’re going to be more prone because 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 program-resolving mediators or SPM’s… And actually have this as a supplement now. These are actually quite fascinating compounds. The SPM’s are selective pro-resolving mediator compounds. They’re basically turbo charged fish oil. And certain people, some people can’t take their omega-3 fatty acids and turn them into these compounds and clinically, I have found them to 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 whose 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.

Dr. Mark Hyman:
Yeah, so true. 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 Dr. 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 the brain. And for brain function. And in any individual-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… the same cause might cause different things. In one person it might cause schizophrenia, in another person it might cause Alzheimer’s, in another person it might cause depression.

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
We really have the tools to look at a true cognoscopy.

Dr. Mark Hyman:
And then the question is how do we help the brain repair? How do we set up the conditions for the brain repair? Let’s talk about how from a Traditional or 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.

Dr. Todd Lepine:
Yeah. As you mentioned, Mark, we do a lot of the testing. So we’ll do organic acid testing which is checking for the nutrient metaboloids that are found in the body. We’ll also do guy microbiome testing looking at all of the different bacterial viruses, yeast, parasites potentially in the body. We’ll look at markers for leaky gut. The other tests that I do is leaky brain. Just like you can have leaky gut, you can have a leaky brain. There’s actually a test for that. Cyrex Laboratories 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 there is like to use is the GI map test because I think it’s quantitative PCR so I find it to be very helpful.

Dr. Todd Lepine:
I think the whole GI realm area is an area that we’re just learning and 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.

Dr. Todd Lepine:
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 will 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, our brain only comprises two percent of our body weight, but it uses 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 like metabolic blood products, misfolded proteins, inflammatory molecules, amyloid, etc., build up in the brain and affect how the person’s cognition is, their memory, their mood, etc.

Dr. Mark Hyman:
It’s amazing. You and I think the diet has such a huge role too in the brain. 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 foods with all the phytochemicals in them and the nutrient dense foods. We’re eating a diet that’s super inflammatory. That’s the first thing. And often dairy and gluten are among the worst.

Dr. Mark Hyman:
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 immune function. Getting adequate levels of these is key.

Dr. Mark Hyman:
Also, we really get people on an elimination diet if we suspect or we test that they have sensitivities to certain foods. We treat the underlying infections if we find them directly with antibiotics if we need to or 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. We have a whole Functional Medicine approach to fixing the gut we’ve talked about a lot on this podcast.

Dr. Mark Hyman:
And then we’ll address whatever toxins that are there and help you eliminate the toxins through a really focused detoxification program. Building on the framework of Functional Medicine, was 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 and people’s lifelong depression gets better.

Dr. Mark Hyman:
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 anymore, 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 vegan-ish diet essentially. And she said at the six-week reunion, she was 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.” She goes “Is that possible?” And I’m like, “Yeah, it’s possible. If whatever you were eating was triggering the inflammation in your brain and you stopped it, yes.”

Dr. Mark Hyman:
It really is untapped reservoir of tools and tests and therapies that Traditional Medicine psychiatry and neurology are just not using. And it’s really where the money is.

Dr. Todd Lepine:
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 examine the patient. And I think that a lot of psychiatrists would actually do a good job if they actually took a side course in neurology to really understand how the brain is working.

Dr. Todd Lepine:
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 my other pet peeve about the psychiatric world is that we are now medicating young children in ways that are unexplored. We’re doing polypharmacy in the young, polypharmacy in the old with these neuropsych drugs. They’re advertised on television. And it is a complete, if you will, (beep) 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 young kids. This is something that we should not be doing. Period.

Dr. Mark Hyman:
No. It’s true. We really are relying on downstream treatments. When the neurotransmitters go awry, whether it’s depression or autism or Alzheimer’s-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… or ADD, 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 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 throughout our bodies. And there’s a key step in converting tryptophan into 5-hydroxytryptophan into serotonin, which is the happy mood chemical. And when you get a high level of inflammation in the body, the enzyme is blocked and you end up with this by-product called kynurenate, I don’t know if I’m pronouncing it right. [inaudible 00:41:01] I said.

Dr. Todd Lepine:
Kynurenic acid. Right.

Dr. Mark Hyman:
Yeah. Kynurenic acid and that level goes up and you can actually measure it in these patients. And you see when they have high levels of these quinolinate or kynurenic acid it indicates inflammation. And you know that the serotonin pathyway’s being screwed up and it’s bypassing it and producing these toxic molecules that cause inflammation in the brain. And so 1) by getting rid of the inflammation and 2) 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.

Dr. Todd Lepine:
It’s interesting that you say that, Mark, because I used to lecture for Metametrix 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 on organic testing. And this compound was actually first isolated in patients who had AIDS dementia. And what they found is that as you mentioned and how that pathway gets switched over, various things like viruses, like the AIDS virus can actually up regulate the production of quinolinic acid. And high levels of quinolinic acid cause the brain to become inflamed, it causes the brain to shrink and they can eventually cause Alzheimer’s or dementia type symptoms. AIDS dementia was basically how we found the importance of quinolinic acid. And 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.

Dr. Mark Hyman:
Yeah. We do. At the UltraWellness Center we definitely do and we see so-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… much from that data-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… that can help us figure out how to help these patients. And that’s really what’s, to me, so exciting.

Dr. Todd Lepine:
I’m going to go back to when I went through my training because I trained at Dartmouth and I had 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 when I did my psychiatric training at Dartmouth, I had another mentor who was board certified both in psychiatry and neurology. That’s where I really got, and he was someone who would actually order tests on patients and understand that let’s try to figure out what’s going on. This was way before Functional Medicine was prominent. And it got my own brain thinking about neuropsychiatry. And it’s a fascinating field. You can’t split them.

Dr. Mark Hyman:
Yeah.

Dr. Todd Lepine:
Neurology and psychiatry are one.

Dr. Mark Hyman:
Yeah.

Dr. Todd Lepine:
And only when you think that they separate, you have this dichotomy. And you’re not going to help neurological patients and you’re not going to help the psych patients. You need to think neuropsychiatrically.

Dr. Mark Hyman:
Well, I’m suer this happened to you like it happened to me, but when I started practicing Functional Medicine, I wasn’t focused on the brain. I wasn’t focused on treating people by dealing with 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-

Dr. Todd Lepine:
Yeah.

Dr. Mark Hyman:
… 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 whatever was going on. And incidentally, their psychiatric problems would get better. Or their ADD would get better. And they’d report “Dr. Hyman, I’m not depressed anymore. My panic attacks are gone. My OCD is better. My memory is better.” I was like, “What’s going on here?” And 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 our patients, you listen to them, they’ll actually tell you what’s going on. I’m like, “Well, something’s going on here.” And that’s truly what led me to write the book The UltraMind Solution, which is how to fix your broken brain by fixing your body first.

Dr. Mark Hyman:
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 then were in the literature, but just really beginning in stuff that I saw clinically like the role of, for example, tick infections. The role of the gut microbiome. Who was 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.” That’s really why I wrote that book.

Dr. Mark Hyman:
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 from a doctor and there’s even sections in there on what to do if you need to go see a doctor, what tests you should ask for. But it really was striking to me.

Dr. Mark Hyman:
And I remember this one patient came in after a while, after it’d written the book, about a year later. And I said, “Oh, why are you here?” She said “Well, I’m pretty good.” And I’m like, “Well, what’s going on?” “Well, a while ago I had all these brain issues and depression, memory issues and blabety blah.” And I’m like “Well why are you here then if you’re better now?” And she was like “Well, I read your book and I followed all the directions and I got better. It took nine months to get an appointment and so maybe you can help me to get even better.” And I’m like “Okay.”

Dr. Mark Hyman:
What was so beautiful about it was that I literally took the science of what we do in Functional Medicine and applied it in a practical step for people to do. And sometimes I maybe 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.

Dr. Mark Hyman:
Again, everybody listening, you’ve been listening to podcast Doctor’s Farmacy, House Call. We’ve been talking about brain on fire, neuroinflammation, [inaudible 00:46:59] 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. 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 Farmacy.

Dr. Mark Hyman:
Hey, this is Dr. Hyman. If you enjoyed this video, you’re going to want to check out this next video coming up. Not only can you have a leaky gut, but you can have a leaky brain.
Speaker 3:
Look, bacteria, not to scare people, but bacteria love the brain. Why? 25% of the body’s glucose is used by the brain. They know where to eat. They’re going to [inaudible 00:47:44].

If you are looking for personalized medical support, we highly recommend contacting Dr. Hyman’s UltraWellness Center in Lenox, Massachusetts today.

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