Latest / Resiliency Radio with Dr. Jill Carnahan, MD / 329: Resiliency Radio with Dr. Jill: The Hidden Drivers of Brain Diseases with Dr. David Perlmutter

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329: Resiliency Radio with Dr. Jill: The Hidden Drivers of Brain Diseases with Dr. David Perlmutter · Resiliency Radio with Dr. Jill Carnahan, MD

• 0:01
  Dr. Jill Carnahan, MD: Welcome to Resiliency Radio, your go to podcast for the most cutting edge insights integrative and functional medicine.
• 0:08
  Dr. Jill Carnahan, MD: I'm your host, Dr. Jill and with each episode we dive into the heart of healing and personal transformation.
• 0:14
  Dr. Jill Carnahan, MD: Join me as I interview world experts, thought leaders and medical developers of all kinds of new technology information to help you thrive and work your way to optimal performance and longevity.
• 0:26
  Dr. Jill Carnahan, MD: Today is a very special episode as we've reached 1 million subscribers.
• 0:31
  Dr. Jill Carnahan, MD: I have brought back one of my favorite guests, Dr. David Pearl Mutter.
• 0:34
  Dr. Jill Carnahan, MD: He has been a fan favorite and today we're going to be talking about his new book, Brain Defenders.
• 0:40
  Dr. Jill Carnahan, MD: You're going to learn all about microglia and why you have control over your brain health.
• 0:45
  Dr. Jill Carnahan, MD: So stay tuned.
• 0:45
  Dr. Jill Carnahan, MD: You will not want to miss this interview.
• 0:47
  Dr. Jill Carnahan, MD: Before we get to the introduction and his bio, I just want to remind you that at Flatiron Functional Medicine, my practice in Lewisville, Colorado, we are accepting new patients.
• 0:56
  Dr. Jill Carnahan, MD: We have a team of people to help you.
• 0:58
  Dr. Jill Carnahan, MD: You can either email info flatiron functional medicine.com or give us a call at 303-993-7910.
• 1:06
  Dr. Jill Carnahan, MD: If you want to schedule a 10 minute free call with one of our providers to see if it's a good fit, we can do that as well.
• 1:12
  Dr. Jill Carnahan, MD: So give us a call 303-993-7910.
• 1:16
  Dr. Jill Carnahan, MD: If you're looking for a functional medicine expert provider and we would love to help you on your journey.
• 1:22
  Dr. Jill Carnahan, MD: Also, if you haven't yet got a copy of my book or seen the movie, you can get that@readunexpected.com you can get a signed copy if you go to my store Dr. Joel health.com and you can watch the movie at doctor patient movie.com or it's on Amazon prime.
• 1:37
  Dr. Jill Carnahan, MD: So if you have a membership you can go to Amazon Prime.
• 1:39
  Dr. Jill Carnahan, MD: Just search Doctor Patient Movie and check it out.
• 1:42
  Dr. Jill Carnahan, MD: I've heard some incredible feedback over the years since its release and I would love to have you take a look.
• 1:47
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• 1:48
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• 1:49
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• 1:54
  Dr. Jill Carnahan, MD: Check it out.
• 1:55
  Dr. Jill Carnahan, MD: Dr.
• 1:55
  Dr. Jill Carnahan, MD: Patient movie.com okay, let's get to our guest.
• 1:59
  Dr. Jill Carnahan, MD: Our guest is Dr. David Pearl Mutter.
• 2:01
  Dr. Jill Carnahan, MD: He is a very well known doctor and author of many books.
• 2:05
  Dr. Jill Carnahan, MD: He's board certified Neurologist, six times New York Times Bestseller who has his work has focused on the intersection of neurology, nutrition and brain health.
• 2:13
  Dr. Jill Carnahan, MD: We're going to be diving deep into brain health today.
• 2:16
  Dr. Jill Carnahan, MD: A Fellow of The American College of Nutrition.
• 2:18
  Dr. Jill Carnahan, MD: He serves on its board of directors, in the editorial board of Journal of Alzheimer's Disease.
• 2:23
  Dr. Jill Carnahan, MD: His books include number one bestseller, Grain Brain, which I found out in this interview, is his number six book.
• 2:28
  Dr. Jill Carnahan, MD: And now he's on number 16, which is brain Defenders.
• 2:31
  Dr. Jill Carnahan, MD: This upcoming book focuses on the pivotal role of microglia, the brain's immune cells, in protecting, repairing, and reprogramming the brain for lifelong resilience.
• 2:42
  Dr. Jill Carnahan, MD: And it's now available for pre order.
• 2:44
  Dr. Jill Carnahan, MD: You will love this interview.
• 2:45
  Dr. Jill Carnahan, MD: Let's get to the show.
• 2:47
  Dr. Jill Carnahan, MD: Dr. Pearl Mutter, it is always my deepest pleasure to have you on the podcast.
• 2:51
  Dr. Jill Carnahan, MD: This is the second time and our first podcast got many views.
• 2:55
  Dr. Jill Carnahan, MD: You're so articulate and you' such a great human as far as just how you bring this information to the world.
• 3:00
  Dr. Jill Carnahan, MD: I know your heart.
• 3:01
  Dr. Jill Carnahan, MD: I know we've sat at dinners before and just shared deep insights into the world.
• 3:06
  Dr. Jill Carnahan, MD: And what I'm so excited today is your new book, which is the accumulation of years and years of research and brings together so many concepts.
• 3:13
  Dr. Jill Carnahan, MD: We're going to dive in today.
• 3:15
  Dr. Jill Carnahan, MD: You guys are going to love this interview.
• 3:17
  Dr. Jill Carnahan, MD: But first, Dr. Perlmutter, tell us a little bit about your journey from Grain brain, or I'm not sure if that was the first one or what happened and then to where you're at now and how we just talked about this may be the accumulation of a lifetime of work.
• 3:31
  Dr. David Perlmutter: Well, first let me say thanks for having me again.
• 3:33
  Dr. David Perlmutter: I feel like we're just picking up our conversation where we left off last time.
• 3:36
  Dr. David Perlmutter: But I think between our last podcast, then we had dinner together and that felt like a continuation of the podcast.
• 3:44
  Dr. David Perlmutter: But Grain Brain was book number six, oddly enough, and this new book, Brain defenders, is number 16.
• 3:51
  Dr. David Perlmutter: So there was a, you know, pretty significant, lots of things happen between Grain Brain and where we are now.
• 3:56
  Dr. David Perlmutter: But I think the point that you're getting at is that finally, with Brain Defenders and this understanding of the fundamental role of the brain's immune system in terms of what will keep our brains working great for the rest of our lives or what sets the stage for brain decline is really what happens.
• 4:16
  Dr. David Perlmutter: And this is central to our conversation today.
• 4:19
  Dr. David Perlmutter: Really what happens to the brain's immune system?
• 4:22
  Dr. David Perlmutter: System.
• 4:22
  Dr. David Perlmutter: The brain's immune system is made up of cells called the microglial cells.
• 4:27
  Dr. David Perlmutter: So the microglia are the cells that we are going to be focused on today deeply.
• 4:32
  Dr. David Perlmutter: And something that you alluded to in the time before you hit the record button was the relationship of how these microglial cells function to Our body's metabolism, they can be either supportive of a great brain, pave the way for synapses to make, you know, good contact one neuron to the next, shore up the blood brain barrier, allow neurons to be in a wonderful working environment, or these exact same cells can shift to become the evil twin.
• 5:02
  Dr. David Perlmutter: We call that the M1 microglial cell, and that's a microglial cell that goes around destroying our synapses, making an environment that does not prove to be conducive to neuronal function, and really destabilizes the really important function of the blood brain barrier.
• 5:19
  Dr. David Perlmutter: The key is that this shift of these brains, immune cells, microglia, from being friend to being foe, the shift from being M2 to being M1, being brain defenders or brain destroyers, is a shift over which you and I and everybody watching us on the podcast today has control.
• 5:41
  Dr. David Perlmutter: We can control our brain's destiny by controlling the factors that influence whether our microglia are on our side or have turned their backs on us.
• 5:52
  Dr. David Perlmutter: And importantly, many of the things that you've been talking about for so long are hugely influential in terms of whether those microglial cells are going to help us have a good brain as we age or not.
• 6:06
  Dr. Jill Carnahan, MD: It makes so much sense.
• 6:07
  Dr. Jill Carnahan, MD: And we used to really just focus on the plaques and this as a target.
• 6:10
  Dr. Jill Carnahan, MD: What we realized is those are just so signs and symptoms, as a good doctor would see, that did show us an underlying issue.
• 6:17
  Dr. Jill Carnahan, MD: Right.
• 6:17
  Dr. Jill Carnahan, MD: And so then we look deeper and deeper.
• 6:19
  Dr. Jill Carnahan, MD: Now we're at this level.
• 6:21
  Dr. Jill Carnahan, MD: And what I love that we talked about right before, and I'd love for you to go on and talk more about this is part of our immune system.
• 6:27
  Dr. Jill Carnahan, MD: Right.
• 6:27
  Dr. Jill Carnahan, MD: And this, I, I, I love the term, the new term that I've heard a lot, and I spoke in Switzerland last year, immune resilience.
• 6:33
  Dr. Jill Carnahan, MD: It's really like, how does the immune system really at the core of all of these metabolic and functional things that we see, do you want to tie in for someone out there being like, okay, first of all, what's a microglia cell?
• 6:43
  Dr. Jill Carnahan, MD: And then what does the immune system have to do with brain health?
• 6:46
  Dr. David Perlmutter: Sure.
• 6:47
  Dr. David Perlmutter: First, the feeling that I had when you were asking that question is we could probably speak for about two or three hours and just have the best time ever.
• 6:55
  Dr. David Perlmutter: But I know for social media they say, oh, you have to limit the length of your podcast or you'll lose viewers, whatever.
• 7:01
  Dr. David Perlmutter: But I think it's that we're recontextualizing the function of the immune system these days.
• 7:09
  Dr. David Perlmutter: I mean, you know, we.
• 7:11
  Dr. David Perlmutter: The general discussion of immunity is, well, we want to have a strong immune system such that when we are challenged by the flu or Covid or whatever it may be or the development of malignancy in the body, that our immune system is going to come to the rescue, suddenly get activated, and the whole cascade of what's involved in an immune response is going to be initiated and propagated such that we can get rid of cancer cells or we can trap that virus so that it's limited in terms of activity.
• 7:38
  Dr. David Perlmutter: And if you don't have a good immune system, then you're going to be a victim a bad viral infection, bacterial infection, or even, you know, cancer overgrowth.
• 7:48
  Dr. David Perlmutter: Because it wasn't limited by the immune system.
• 7:51
  Dr. David Perlmutter: But now we've really broadened our scope in terms of understanding what the immune system does.
• 7:57
  Dr. David Perlmutter: It's a lot more involved in maintenance than simply in.
• 8:02
  Dr. David Perlmutter: In terms of response to a challenge.
• 8:05
  Dr. David Perlmutter: So a great metaphor is that, yeah, we know when there's a fire, the fire engine is going to, you know, come with sirens blazing and take care of the fire.
• 8:14
  Dr. David Perlmutter: That's how we used to think about the immune system.
• 8:16
  Dr. David Perlmutter: But I think now we're going to be realizing that, you know, 90% of the time, the fire engine's in the firehouse.
• 8:22
  Dr. David Perlmutter: But what's happening then is that the firemen, the technicians, are making sure that it's working well.
• 8:29
  Dr. David Perlmutter: They're, you know, changing the oil and buffing it up and making sure that the mechanics are working as best they can.
• 8:36
  Dr. David Perlmutter: And that's really an extension, I think, of our understanding of what the immune system does certainly in the brain.
• 8:42
  Dr. David Perlmutter: That, yes, these microglial cells are the brain's immune defense system that go into action when we need them, when the brain is challenged.
• 8:51
  Dr. David Perlmutter: But they're also there for maintenance and nurturing and keeping our neurons in their optimal condition so they can perform as best they can.
• 9:00
  Dr. David Perlmutter: And keeping our synapses, which are so vital for brain function, one neuron connecting to the next through the dendrites, keeping those synapses not only working well and functional, but also nurturing the growth of new synapses such that we are able to learn new information.
• 9:18
  Dr. David Perlmutter: That is the task of the microglial cell.
• 9:20
  Dr. David Perlmutter: So, you know, fundamentally, we embrace a much wider net that the immune system is able to throw.
• 9:27
  Dr. David Perlmutter: Yes, it comes online during times of challenge, but it's really involved throughout the body and even in the joints in terms of keeping these tissues in their optimal level of functionality.
• 9:40
  Dr. David Perlmutter: So that's what these Microglial cells do.
• 9:43
  Dr. David Perlmutter: And we want to keep.
• 9:44
  Dr. David Perlmutter: We want to do everything we can so that their nurturing role is nurtured by us and importantly, our metabolic choices.
• 9:54
  Dr. David Perlmutter: How we eat, how much exercise we get, the quality and quantity of our sleep, our social interaction, which we really should unpack at some point, the level of stress that we engage each day, all of these things are looked upon by our microglial cells.
• 10:08
  Dr. David Perlmutter: They're watching.
• 10:09
  Dr. David Perlmutter: And if we are eating inappropriately and we increase inflammation or our blood sugar rises, the microglial cells will turn their backs on us.
• 10:18
  Dr. David Perlmutter: They'll say, this isn't what we want.
• 10:20
  Dr. David Perlmutter: And they become the evil twin.
• 10:22
  Dr. David Perlmutter: They go about digesting away our synapses.
• 10:26
  Dr. David Perlmutter: That's not a good thing.
• 10:27
  Dr. David Perlmutter: And, and yet take home message again, we can control that love ending there.
• 10:33
  Dr. Jill Carnahan, MD: As far as this moment of discussion, because I think we have come from a society with a patriarchal medical system where you go, you get the prescription, you get the doctor's orders, and then you're really this like, receiver of the great wisdom, right?
• 10:47
  Dr. Jill Carnahan, MD: And now that we have learned and grown, and hopefully you and I in clinic, and any good doctor is actually just a partner with the patient, giving them a roadmap to a destination that they both together want to go to.
• 10:58
  Dr. Jill Carnahan, MD: And what you're saying with the brain is we have a clear roadmap to good brain health.
• 11:02
  Dr. Jill Carnahan, MD: And whether you have APOE 44 or not, or any other, the issues that could lead to things like Alzheimer's or neurodegenerative diseases, you still, no matter what genetics you were handed, have choice in the matter.
• 11:15
  Dr. Jill Carnahan, MD: I want to talk about immunometabolism and all these other terms, but before we do, let's just talk a little bit more about the ability to control our destiny.
• 11:24
  Dr. Jill Carnahan, MD: And what are like, you already named some of the key factors, but what are some of the things, toxins, infections, lifestyle, that really do matter in microgl Health.
• 11:33
  Dr. David Perlmutter: Let's unpack those.
• 11:34
  Dr. David Perlmutter: But I, I don't want what you just said to be passed by because it's so important and that is that we do have the agency to control our brain's destiny.
• 11:46
  Dr. David Perlmutter: We could end at that point.
• 11:47
  Dr. David Perlmutter: And that.
• 11:48
  Dr. David Perlmutter: Because that's the take, that's the bullet point because you alluded to this a moment ago that, you know, you go to the doctor and it's a very disempowering experience that in.
• 12:03
  Dr. David Perlmutter: First you're told, basically, live your life however you choose, then we will figure out your problem and Tell you what to do.
• 12:09
  Dr. David Perlmutter: Well, as it relates to brain degeneration and specifically Alzheimer's, there is no we will tell you what to do available.
• 12:17
  Dr. David Perlmutter: There is no pharmaceutical fix that has any meaningful benefit as it relates to treating the patient wants he or she, mostly she, two thirds are female, are diagnosed with this disease.
• 12:29
  Dr. David Perlmutter: Though there are strangely FDA approved drugs that are marketed and used in the clinical practice to so called treat Alzheimer's disease.
• 12:41
  Dr. David Perlmutter: And gets back to something you mentioned a few minutes ago, and that is that there is still this misguided sense that Alzheimer's is caused by the accumulation of this abnormally folded protein in the brain called beta amyloid.
• 12:56
  Dr. David Perlmutter: That is patently wrong.
• 12:58
  Dr. David Perlmutter: It is absolutely untrue.
• 13:01
  Dr. David Perlmutter: And here's a reason, among many that I can tell you, and there are several we should talk about why it is untrue.
• 13:09
  Dr. David Perlmutter: And at first it's not just that your guest on the podcast today is saying this.
• 13:13
  Dr. David Perlmutter: A couple months ago there was a Cochrane analysis done, which you know, you and I know are these types of analyses are the gold standard that we use.
• 13:22
  Dr. David Perlmutter: They're unbiased.
• 13:22
  Dr. David Perlmutter: They look at questions that we have in medical science and try to apply the latest evaluation techniques to come up with answer.
• 13:30
  Dr. David Perlmutter: And here's the question, do the Alzheimer's drugs that target beta amyloid work?
• 13:37
  Dr. David Perlmutter: That's a fair question.
• 13:39
  Dr. David Perlmutter: Why?
• 13:39
  Dr. David Perlmutter: Because that's the go to approach for mainstream neurology here in America.
• 13:43
  Dr. David Perlmutter: Do these drugs, these monoclonal antibodies that absolutely help reduce the beta amyloid in the brain, that do they work as it relates to the decline that Alzheimer's patients experience?
• 13:54
  Dr. David Perlmutter: And the answer is no.
• 13:57
  Dr. David Perlmutter: 17 Studies, 20,342 individuals, each study lasting 18 months, looking at two things.
• 14:06
  Dr. David Perlmutter: Do the drugs work and are they hurting people?
• 14:09
  Dr. David Perlmutter: Well, let's look at the second part of that question.
• 14:11
  Dr. David Perlmutter: First of all, 20 to 25% of people who receive these drugs experience brain hemorrhages and or swelling in their brains.
• 14:21
  Dr. David Perlmutter: Now what the drug manufacturers are telling us is, well, yes, they do.
• 14:24
  Dr. David Perlmutter: We know that's a well described risk, but we're not sure if that's hurting anybody.
• 14:30
  Dr. David Perlmutter: I kind of have the feeling maybe I'm off base that bleeding into your brain and swelling aren't necessarily what we want, they're not necessarily good things.
• 14:39
  Dr. David Perlmutter: And did I mention death as well?
• 14:43
  Dr. David Perlmutter: So the risk I think is significant.
• 14:45
  Dr. David Perlmutter: What about the benefit?
• 14:46
  Dr. David Perlmutter: Well, what the Cochrane analysis of 17 studies of these drugs demonstrated, their word was the effectiveness is trivial.
• 14:55
  Dr. David Perlmutter: That is these drugs have no meaningful effect on the progressive downhill slide that Alzheimer's patients experience as a consequence of this disease, even though the drugs do significantly reduce the load of beta amyloid in the brain, that's demonstrated.
• 15:14
  Dr. David Perlmutter: So we've got to look upstream, as you talked about earlier, to what's going on long before the beta amyloid begins to accumulate.
• 15:22
  Dr. David Perlmutter: And what happens decades before are the metabolic shifts in the human body that target these microglial cells.
• 15:31
  Dr. David Perlmutter: In the brain.
• 15:32
  Dr. David Perlmutter: These metabolic shifts take the form of insulin resistance, elevated blood sugar, elevated blood pressure, accumulating too much body fat.
• 15:41
  Dr. David Perlmutter: That occurs in our 40s and 50s, long before we forget grandchildren's names, birthdays and wi fi codes.
• 15:50
  Dr. David Perlmutter: So that's when modern medicine comes into action, when the fire has already begun.
• 15:56
  Dr. David Perlmutter: We're going to try to figure out something we can do to put that fire out now that this individual is having cognitive failure.
• 16:03
  Dr. David Perlmutter: But the problem, as mentioned, begins decades earlier when the metabolic challenges become evident, that blood sugar starts to creep up, that fasting insulin level is increased, the A1C is increased, the homocysteine levels increase.
• 16:17
  Dr. David Perlmutter: And a test you get very frequently, your blood pressure is climbing and you're having to open your belt to another hole on the belt because you're gaining weight.
• 16:27
  Dr. David Perlmutter: Everybody knows these things are happening.
• 16:30
  Dr. David Perlmutter: That's when we've got to be acting.
• 16:33
  Dr. David Perlmutter: I've said this many times that John Kennedy said in his inaugural address that the time to fix the roof is when the sun is shining, not when.
• 16:41
  Dr. David Perlmutter: Now.
• 16:42
  Dr. David Perlmutter: We're experiencing these so called laugh them off senior moments.
• 16:47
  Dr. David Perlmutter: That's long down the continuum.
• 16:49
  Dr. David Perlmutter: We've got to act in a preventive way to keep the brain functional.
• 16:54
  Dr. David Perlmutter: And what happens early on is this shift in these microglial cells away from being supportive to being threatening brought on by the very things we're talking about, these lifestyle choices that play out as changes in human metabolism.
• 17:10
  Dr. Jill Carnahan, MD: Hey guys, just a quick moment to interrupt the show and remind you can get all great products and services for brain health@doctor health.com you can get a discount off your first purchase.
• 17:19
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• 17:24
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• 17:29
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• 17:34
  Dr. Jill Carnahan, MD: Check it out@doctor Joel health.com okay, let's get back to our show.
• 17:39
  Dr. Jill Carnahan, MD: So this key concept is one of the main thing in Brain defenders and that's this concept of immunometabolism, this core integration of our Immune system, our metabolic system, the pre diabetic.
• 17:50
  Dr. Jill Carnahan, MD: And what you're saying, if I can repeat this just for our listeners to really get this clear, is that someone in their even late 20s, early 30s and 40s is starting that process towards degeneration of the microglia or over activation in the synaptic pruning or whatever is happening in that immune reaction.
• 18:07
  Dr. David Perlmutter: It is.
• 18:07
  Dr. Jill Carnahan, MD: Right?
• 18:08
  Dr. David Perlmutter: You nailed it.
• 18:09
  Dr. David Perlmutter: You absolutely nailed it.
• 18:10
  Dr. David Perlmutter: That you know, that's what goes on in the brain when the microglia are activated.
• 18:15
  Dr. Jill Carnahan, MD: Yes.
• 18:15
  Dr. David Perlmutter: We abnormally increase the rate of digestion or removal of our synapses.
• 18:22
  Dr. Jill Carnahan, MD: I love that we're pruning, by the way, because you can just see, imagine a bush and over pruning it, right.
• 18:26
  Dr. Jill Carnahan, MD: And it starts to die off.
• 18:27
  Dr. Jill Carnahan, MD: And it's a great word that has been.
• 18:30
  Dr. David Perlmutter: It absolutely is.
• 18:31
  Dr. David Perlmutter: Well, you know, there is a time when that pruning of the synapses is totally appropriate.
• 18:35
  Dr. David Perlmutter: When we're, you know, young children up into our middle teens, we do in fact have a higher rate of synaptic loss.
• 18:41
  Dr. David Perlmutter: But that's a process of brain refinement, making the brain more streamlined, making it more efficient.
• 18:47
  Dr. David Perlmutter: And that's vital.
• 18:48
  Dr. David Perlmutter: When you don't have that process occurring as it should, which is mediated by the microglial cells, the brain remains over connected, hyperconnected and hyperconnected.
• 18:59
  Dr. David Perlmutter: And that is what characterizes the brain in Autism spectrum disorder.
• 19:03
  Dr. David Perlmutter: So we have to have that right level of pruning.
• 19:06
  Dr. David Perlmutter: But what Alzheimer's represents is a reactivation of this normal developmental process of synaptic pruning by over activation of the microglial cells because they have become metabolically challenged and because they are responding to inflammation in the body.
• 19:25
  Dr. David Perlmutter: And again, we have the tools to control that.
• 19:28
  Dr. David Perlmutter: And let me just say that, you know, certainly in Brain Defenders, I talk about, you know, why we need to control our blood sugar and reduce inflammation.
• 19:36
  Dr. David Perlmutter: Pay attention to the gut brain connection, that is the microbiome.
• 19:41
  Dr. David Perlmutter: But interestingly, we review what is the technology right now, what is the research showing us and where are even pharmaceutical companies looking in terms of really novel ways of controlling the microglia, kind of gratefully abandoning the beta amyloid targeted therapies and saying, you know, that hasn't paid off.
• 20:04
  Dr. David Perlmutter: Albert Einstein said that insanity, the definition of insanity, is doing the same thing over and expecting different outcome.
• 20:11
  Dr. David Perlmutter: You can slice it however you want and the beta amyloid drugs are not going to work.
• 20:17
  Dr. David Perlmutter: But targeting metabolism does work.
• 20:19
  Dr. David Perlmutter: So what does it mean?
• 20:21
  Dr. David Perlmutter: I'm all in as it relates to the possibility that a GLP1 agonist drug, an Ozempic like drug, because that's a powerful approach to regulating metabolism, might prove helpful in Alzheimer's.
• 20:35
  Dr. David Perlmutter: We've seen a study published in May of 2024 in the New England Journal of Medicine where the use of a GLP1 drug, an Ozempic like drug, arrested Parkinson's.
• 20:45
  Dr. David Perlmutter: Disease progression, dead in its tracks.
• 20:48
  Dr. David Perlmutter: In other words, the people taking this drug versus placebo, they did not decline in their function over the course of one year versus the expected decline in the placebo group.
• 21:00
  Dr. David Perlmutter: Now, 42% of these individuals had nausea and other gastrointestinal issues.
• 21:05
  Dr. David Perlmutter: I get that.
• 21:07
  Dr. David Perlmutter: But it means we.
• 21:07
  Dr. David Perlmutter: We've got to keep looking.
• 21:09
  Dr. David Perlmutter: There may well be, you know, an approach using a GLP1 agonist drug.
• 21:13
  Dr. David Perlmutter: Now, maybe you think I'm off topic, and maybe your viewers right now are saying, well, Dr. Perlman is now talking about a drug, and that's unlike him.
• 21:22
  Dr. David Perlmutter: That's not my mission.
• 21:24
  Dr. David Perlmutter: My mission is to look at every possible tool that could have that, through which we.
• 21:29
  Dr. David Perlmutter: We evaluate risk and benefit.
• 21:32
  Dr. David Perlmutter: And maybe that's something we put in the toolbox, because basically, you know, Alzheimer's is uniformly a fatal condition.
• 21:40
  Dr. David Perlmutter: We all know a cancer survivor.
• 21:42
  Dr. David Perlmutter: How many Alzheimer's survivors do we know?
• 21:45
  Dr. David Perlmutter: And so the idea that we would want to pull out the stops and use a medication that, you know, may be committing this person to using this GLP1 drug for the rest of his or her life, I'm willing to consider that.
• 21:58
  Dr. David Perlmutter: And in other words, interesting technologies that are now being developed.
• 22:02
  Dr. David Perlmutter: Microglial transplant to the human brain.
• 22:06
  Dr. David Perlmutter: It's already been done.
• 22:07
  Dr. David Perlmutter: Mitochondrial transplant flashing a light at 40 hertz.
• 22:11
  Dr. David Perlmutter: Dr. Li, Wei Tsai's work at MIT to reduce the activation of microglia.
• 22:17
  Dr. David Perlmutter: There's a lot of stuff out there that's so exciting.
• 22:20
  Dr. David Perlmutter: But for now, each and every one of us, through what you've described, immunometabolism, targeting, metabolism part we can affect, immune part, that's the microglial cells.
• 22:31
  Dr. David Perlmutter: We can make the changes today, this afternoon, go for a walk tonight, get a good night's sleep, turn the TV off earlier, get off your computer.
• 22:40
  Dr. David Perlmutter: All the things, right, that we've talked about.
• 22:43
  Dr. David Perlmutter: Who knew that these are front and center, the leverage points that we can pull in order to redirect our brain's destiny.
• 22:53
  Dr. David Perlmutter: It's pretty darn empowering.
• 22:55
  Dr. Jill Carnahan, MD: It's amazing.
• 22:56
  Dr. Jill Carnahan, MD: And you were not off topic at all, because before you had mentioned GLP1, I was thinking, okay, we got to talk about GLP1s.
• 23:03
  Dr. Jill Carnahan, MD: A lot of My podcast listeners have heard me talk to some of the mast cell experts in some of the articles that are case studies.
• 23:08
  Dr. Jill Carnahan, MD: And all of us in that field of mast cell activation, which is just another part of the immune system, have seen pretty profound benefits at very low doses with GLP1.
• 23:17
  Dr. Jill Carnahan, MD: So we already know in case studies, and I think clinical research will prove this out over time, that there is a profound effect on the immune system.
• 23:24
  Dr. Jill Carnahan, MD: We don't know yet exactly why, but your concept of immunometabolism makes that case because it's all connected.
• 23:32
  Dr. Jill Carnahan, MD: So I couldn't agree more that just in entertaining that idea and what I've personally found in clinical experience is that very low doses often give a beneficial effect with very few side effects.
• 23:42
  Dr. Jill Carnahan, MD: And I'm finding some of those things shifting, especially in my mast cell patients, which, again, is just a sentinel of the other immune parts that are being overactivated and could be affecting the brain as well.
• 23:53
  Dr. David Perlmutter: Yeah, let me comment on that, because my senses, and I think we can look at the literature, but my sense is that what's going wrong in terms of mast cell activation is that in order for mast cells to do what they need to do for health and not degranulate and not release these neurotransmitters is they need to have good metabolic function.
• 24:17
  Dr. David Perlmutter: Their mitochondria need to be functioning better.
• 24:20
  Dr. David Perlmutter: And I think that mast cell activation syndrome may well represent a deficiency of energy production in the mast cell as a consequence of a mitochondrial dysfunction.
• 24:32
  Dr. David Perlmutter: That may sound a little bit into the weeds, but I bet some of your viewers are going, yeah, that makes a lot of sense, I hope.
• 24:36
  Dr. David Perlmutter: Anyway, so, you know, with these GLP1 agonist drugs, what we are seeing is a pretty robust enhancement of mitochondrial energy production.
• 24:48
  Dr. David Perlmutter: And why it interests me is the main issue that is seen to be involved in the shift of the brain's microglial cells from being supportive brain defenders to being destructive.
• 25:01
  Dr. David Perlmutter: What I call the evil twin is a loss of energy production from the mitochondria.
• 25:09
  Dr. Jill Carnahan, MD: Yes.
• 25:10
  Dr. David Perlmutter: So this can be a consequence of metabolism issues like elevated blood sugar, insulin resistan, or the microglia sensing inflammatory chemicals, or it can be the cause.
• 25:24
  Dr. David Perlmutter: For example, we've seen that when people are exposed to mitochondrial toxins, it leads to microglial cell activation that can destroy the part of the brain that makes dopamine for motor function.
• 25:38
  Dr. David Perlmutter: And we've known for an awful long time that we see it in experimental animal.
• 25:43
  Dr. David Perlmutter: For example, if you want to produce Parkinson's in the experimental animal, you give them a Mitochondrial toxin.
• 25:49
  Dr. David Perlmutter: You give them paraquat, for example, and you can make a primate have Parkinson's disease almost immediately.
• 25:56
  Dr. David Perlmutter: That's paraquat.
• 25:58
  Dr. David Perlmutter: That's the weed killer that now is being used in America on the crops that we eat.
• 26:06
  Dr. David Perlmutter: I'll let that one hang around for just a little while.
• 26:08
  Dr. David Perlmutter: We know that glyphosate is a mitochondrial toxin as well.
• 26:12
  Dr. David Perlmutter: So it's interesting because I interviewed on my podcast and it airs today, a Dr. Ray Dorsey, who's written a couple of books about how Parkinson's is a man made disease, that we are exposing ourselves to mitochondrial toxins.
• 26:27
  Dr. David Perlmutter: But again, getting back to mast cell activation, we know that B vitamin deficiency has a role to play there as well.
• 26:35
  Dr. David Perlmutter: But I suspect it's an energetic issue related to mitochondrial function.
• 26:38
  Dr. David Perlmutter: And that would explain why the GLP1s are getting attention in mast cell activation syndrome.
• 26:44
  Dr. Jill Carnahan, MD: That makes so much sense.
• 26:45
  Dr. Jill Carnahan, MD: And like I said, I think as we look at the metabolic system, whether it's diet or lifestyle or movement or connection or all of those things that we already know, and then we thought were open minded to new peptides and things that are shifting this, I think we're going to find new solutions by being open minded to that which.
• 27:00
  Dr. Jill Carnahan, MD: I agree with you.
• 27:02
  Dr. Jill Carnahan, MD: So two terms that are being thrown out there a lot, and I've spoken about them and so have you, but I wanted to find them for the audience because they're relevant to the brain and the brain defenders, and that is immunosenescence and inflammaging.
• 27:13
  Dr. Jill Carnahan, MD: These are kind of popular terms that people may have heard of, and you just alluded to immunosenescence.
• 27:18
  Dr. Jill Carnahan, MD: But do you want to define those and talk a little bit about why that's also very relevant to the microglia?
• 27:24
  Dr. David Perlmutter: Yeah, well, as it relates to inflammation, it's a term that really centers upon the primary fundamental role of inflammation that can have its origin anywhere in the body in terms of the aging process.
• 27:41
  Dr. David Perlmutter: So we could go deep into that in terms of the epigenetic markers that relate to aging and how they are enhanced in the presence of inflammation.
• 27:52
  Dr. David Perlmutter: Let's go there for just one moment because we now see that our concept of how we can metricize aging, how we can look upon aging, has really gone a lot further than simply telomere length that we're now using these epigenetic clocks.
• 28:10
  Dr. David Perlmutter: We're looking at the marks upon our DNA that regulate DNA expression.
• 28:16
  Dr. David Perlmutter: But these methylation marks upon our DNA, called epigenetic marks, can be measured and can be correlated with what is now called our biological aging, and not just what our biological versus chronological age is right now, but even using, for example, the Dunedin clock, the rate at which that aging is occurring, we know that inflammation has a dramatic effect upon the accumulation of these epigenetic markers that are then measurable.
• 28:47
  Dr. David Perlmutter: So there's this direct relationship then, between the presence of inflammation in the body and the rate at which the body is going to age.
• 28:56
  Dr. David Perlmutter: From a biological perspective, chronologically, that means simply the number of laps we've had around the sun every year.
• 29:02
  Dr. David Perlmutter: How many birthdays have you had, really?
• 29:04
  Dr. David Perlmutter: Very, I think, irrelevant as it relates to what you're interested in and even medical research.
• 29:10
  Dr. David Perlmutter: Why we use chronological age in medical research and in the determination of who should have this intervention or this type of drug makes very little sense.
• 29:19
  Dr. David Perlmutter: Mutter of fact, there's an interesting editorial in New England Journal of Medicine recently that talked about, no, we should be using biological aging now that these clocks are so widely available.
• 29:28
  Dr. David Perlmutter: I mean, I'm sure you've had your biological age determined, as have I.
• 29:33
  Dr. David Perlmutter: But that said, inflammation is a huge inroad in terms of what makes us age more quickly and as it relates to the brain.
• 29:40
  Dr. David Perlmutter: Absolutely fundamental.
• 29:41
  Dr. David Perlmutter: We covered it earlier.
• 29:42
  Dr. David Perlmutter: Inflammation anywhere in the body activates the microglial cells and shifts them from being friend to foe.
• 29:51
  Dr. David Perlmutter: And that is caused by a change in their epigenetics.
• 29:55
  Dr. David Perlmutter: So we are changing DNA expression of our vital brain immune cells based upon the foods that we eat.
• 30:06
  Dr. David Perlmutter: Wow.
• 30:06
  Dr. Jill Carnahan, MD: Wow, Right.
• 30:07
  Dr. David Perlmutter: Why?
• 30:08
  Dr. David Perlmutter: So how does that work?
• 30:09
  Dr. David Perlmutter: Well, the foods we eat are influential in terms of levels of inflammation in our bodies, the levels of blood sugar, how our insulin is working, the glycation of our proteins.
• 30:21
  Dr. David Perlmutter: All of these things are sensed by these microglial cells in.
• 30:26
  Dr. David Perlmutter: Yes, even the binding of sugar to proteins is sense.
• 30:30
  Dr. David Perlmutter: We have receptors for advanced glycation, end products, rage receptors on the microglial cells.
• 30:38
  Dr. David Perlmutter: We have receptors for inflammatory cytokines that inflammation can come from leaky gut.
• 30:43
  Dr. David Perlmutter: Yeah, we've known a long time that there's a gut brain connection.
• 30:47
  Dr. David Perlmutter: I wrote a book years ago called Brain Maker.
• 30:49
  Dr. David Perlmutter: We talked about the gut brain connection.
• 30:51
  Dr. David Perlmutter: And, you know, the general public thought that was a great book.
• 30:55
  Dr. David Perlmutter: A lot of my colleagues thought that, you know, that Perlmutter is way out there.
• 31:00
  Dr. David Perlmutter: And now everybody kind of throws the term around quite readily.
• 31:03
  Dr. David Perlmutter: Gut brain connection.
• 31:05
  Dr. David Perlmutter: And very soon, I think mainstream medicine will adopt an understanding and use of the term immunometabolism.
• 31:12
  Dr. David Perlmutter: That's the home run.
• 31:13
  Dr. David Perlmutter: That's the convergence of everything you have been talking about.
• 31:16
  Dr. David Perlmutter: And I've Been talking about so many of our colleagues have been really good.
• 31:20
  Dr. David Perlmutter: Getting to the point of embracing for so long the relationship between our metabolism and the immune function, that opens up a lot of opportunity for us because if our immune system is highly influenced by our state of metabolic health, that's, you know, home run, then we can influence everything we're talking about today by making changes in lifestyle that affect our metabolic set point.
• 31:48
  Dr. David Perlmutter: So, yeah, this is all about empowering.
• 31:51
  Dr. David Perlmutter: It's all about, I think, for people to really be empowered and think they're going to move ahead and make not all the changes, but, you know, the lion's share, the ones that are really valuable.
• 32:03
  Dr. David Perlmutter: They have to understand that this is science based and it's reality.
• 32:07
  Dr. David Perlmutter: And the notion to get back to your original point of basically living your life come up may, and then having the doctor walk into the room and say, here's what we're going to put you on.
• 32:17
  Dr. David Perlmutter: I wish it were true, you know, I would have used a drug in my father's case of Alzheimer's.
• 32:24
  Dr. David Perlmutter: None was available then, none is available now.
• 32:27
  Dr. David Perlmutter: Am I hoping there's an Alzheimer's drug?
• 32:29
  Dr. David Perlmutter: Yeah, you bet I am.
• 32:31
  Dr. David Perlmutter: But let's do what we can now.
• 32:33
  Dr. David Perlmutter: And one other comment that came to mind earlier, and I'm just remembering it now, is, you know, were talking about targeting people in their 30s and 40s and yeah, that's where it needs to happen.
• 32:43
  Dr. David Perlmutter: But, you know, when we see what we used to call adult onset diabetes, now we just Simply call type 2 diabetes.
• 32:51
  Dr. David Perlmutter: The reason the change was made is because we are seeing this in adolescents, teenagers, young children getting this diabetes thing when they're 10 years old.
• 33:01
  Dr. David Perlmutter: That sets the stage for Alzheimer's, like it or not.
• 33:04
  Dr. David Perlmutter: So when do we begin this program?
• 33:08
  Dr. David Perlmutter: It really might be at birth, maybe it's even at time of conception.
• 33:13
  Dr. Jill Carnahan, MD: Preconception, right?
• 33:14
  Dr. David Perlmutter: Yeah, you bet.
• 33:16
  Dr. David Perlmutter: Absolutely.
• 33:17
  Dr. David Perlmutter: We mark our genes, our epigenetic markers happen at, you know, right during gestation.
• 33:23
  Dr. David Perlmutter: So that's a little much for.
• 33:25
  Dr. David Perlmutter: I didn't cover it in this book.
• 33:27
  Dr. Jill Carnahan, MD: Yeah.
• 33:27
  Dr. David Perlmutter: But, you know, these points that I'm making, I think for whatever reason, let me just say that this.
• 33:35
  Dr. David Perlmutter: We've gotten a lot of traction this time around on Brain Defenders.
• 33:40
  Dr. David Perlmutter: We've sold this book now to 16 countries around the world.
• 33:42
  Dr. David Perlmutter: Means 16 languages, like Romanian.
• 33:46
  Dr. Jill Carnahan, MD: Wow.
• 33:47
  Dr. David Perlmutter: And I have no way of assessing when I get the Romanian copy.
• 33:51
  Dr. David Perlmutter: Are they really?
• 33:51
  Dr. David Perlmutter: Is this a good.
• 33:53
  Dr. David Perlmutter: I don't know.
• 33:55
  Dr. David Perlmutter: But the idea that, you know, globally people are realizing that brain health is not where it needs to Be and getting worse.
• 34:03
  Dr. David Perlmutter: Yeah, that doesn't speak.
• 34:04
  Dr. David Perlmutter: It speaks to two things.
• 34:05
  Dr. David Perlmutter: First, people are aware of that, want to do something.
• 34:07
  Dr. David Perlmutter: And second, that means it's not genetic.
• 34:11
  Dr. David Perlmutter: If it were genetic, there'd be a baseline rate of these diseases that wouldn't change with time.
• 34:17
  Dr. David Perlmutter: But it's getting worse with time, especially Parkinson's.
• 34:20
  Dr. David Perlmutter: Dramatic increase.
• 34:21
  Dr. David Perlmutter: And that's a consequence of our environmental exposures.
• 34:25
  Dr. David Perlmutter: It means that it's related to changes in terms of what we're exposed to and what we are doing day to day with our lives.
• 34:32
  Dr. David Perlmutter: And the purpose of Brain Defenders is to.
• 34:36
  Dr. David Perlmutter: Is to really give you the tools to the kingdom, the keys to the kingdom, so that you can, you know, you can make these changes now and not whether you're apoe4 you mentioned earlier or not, really dramatically reduce your risk.
• 34:51
  Dr. David Perlmutter: It is not a genetically determined disease carrying the ApoE4 allele.
• 34:58
  Dr. David Perlmutter: Yeah, it increases risk.
• 35:00
  Dr. David Perlmutter: It's not a determinant.
• 35:01
  Dr. David Perlmutter: It's a predisposition that we can absolutely offset with diet and lifestyle change.
• 35:08
  Dr. David Perlmutter: And this is published research.
• 35:10
  Dr. David Perlmutter: This isn't anything you and I are hoping for on this podcast today.
• 35:14
  Dr. David Perlmutter: It's been published.
• 35:15
  Dr. Jill Carnahan, MD: Yes.
• 35:16
  Dr. Jill Carnahan, MD: Oh, this is so good.
• 35:17
  Dr. Jill Carnahan, MD: So full of great information.
• 35:18
  Dr. Jill Carnahan, MD: A couple of things before we end.
• 35:20
  Dr. Jill Carnahan, MD: I want to really talk about one of my favorite topics, and you've just alluded to it.
• 35:24
  Dr. Jill Carnahan, MD: You've alluded to it with the glyphosate and paraquat, but environmental medicine, you bring to light the power of our environment over our brain health.
• 35:31
  Dr. Jill Carnahan, MD: And it could be heavy metals or mold toxicity, which is a particular interest of mine, or many other environmental toxic exp.
• 35:38
  Dr. Jill Carnahan, MD: And what I've witnessed is, over my 20 plus years of practice, it's exponentially increasing talk just a little bit about why the environment matters and why if we're just sitting around not thinking about clean air, clean water, clean food, we're behind the eight ball.
• 35:51
  Dr. Jill Carnahan, MD: And we really need to put that as part of our intervention for brain health.
• 35:56
  Dr. David Perlmutter: In a.
• 35:56
  Dr. David Perlmutter: In a few words, the microglia are sensitive to the very environmental challenges that you just described.
• 36:05
  Dr. David Perlmutter: When we are exposed, the microglia shift.
• 36:09
  Dr. David Perlmutter: It's that simple.
• 36:10
  Dr. Jill Carnahan, MD: Yeah.
• 36:10
  Dr. David Perlmutter: So everything that you've talked about for years as relates to mold and the PM2.5s and the glyphosate paraquat, you know, all of these things that we're exposed to are our inroads to shifting the microglia.
• 36:24
  Dr. David Perlmutter: So again, it's so fascinating for me that we could look through all this stuff through the lens of the microglia and finally get it?
• 36:31
  Dr. David Perlmutter: It's like finding that.
• 36:32
  Dr. David Perlmutter: That piece of this jigsaw puzzle that you've been.
• 36:35
  Dr. David Perlmutter: You know, it has a little blue or a little yellow and part of somebody's hat.
• 36:38
  Dr. David Perlmutter: You go, I'm looking through all these pieces.
• 36:40
  Dr. David Perlmutter: I can't find it.
• 36:41
  Dr. David Perlmutter: I'm only saying that because we just.
• 36:43
  Dr. David Perlmutter: Somebody sent us a jigsaw puzzle that they had made of a bunch of our family photos.
• 36:48
  Dr. David Perlmutter: It was so much fun.
• 36:49
  Dr. David Perlmutter: My wife and I did this.
• 36:49
  Dr. David Perlmutter: Took us like a week.
• 36:52
  Dr. David Perlmutter: Thousands of pieces, but anyway.
• 36:53
  Dr. Jill Carnahan, MD: Yeah.
• 36:54
  Dr. David Perlmutter: And you know how rewarded you feel when you find that piece?
• 36:56
  Dr. David Perlmutter: Well, the microglia have been that piece for me because it unites the gut brain connection inflammation, the effectiveness and beauty of what happens when we exercise.
• 37:07
  Dr. David Perlmutter: Why activating the brain's lymphatic system with deep sleep is so important, how social connectivity is so important.
• 37:15
  Dr. David Perlmutter: I didn't.
• 37:16
  Dr. David Perlmutter: You know, we knew the epidemiology of it.
• 37:18
  Dr. David Perlmutter: We knew the blue zones where people were hanging out with each other and they had less Alzheimer's.
• 37:22
  Dr. David Perlmutter: Great.
• 37:22
  Dr. David Perlmutter: So we can say, okay, we should be interacting with each other.
• 37:25
  Dr. David Perlmutter: That's great.
• 37:26
  Dr. David Perlmutter: But then you ask, well, why, Right?
• 37:29
  Dr. David Perlmutter: What's the mechanism here?
• 37:30
  Dr. David Perlmutter: Why is hanging out with other people a good thing?
• 37:34
  Dr. David Perlmutter: And it turns out that on the microglia there are receptors that tend to keep these microglia cells in their loving, nurturing phenotype where they're preserving the synapses in the neurons.
• 37:47
  Dr. David Perlmutter: And these receptors are receptors for oxytocin.
• 37:53
  Dr. David Perlmutter: Think about that.
• 37:53
  Dr. David Perlmutter: The love hormone that we increase when we are with people we love and feeling that emotion.
• 38:02
  Dr. David Perlmutter: It explains now what I didn't understand before, why people who have been married have a lower rate risk rather of Alzheimer's.
• 38:13
  Dr. David Perlmutter: Even if you've been married and you lose your spouse, you have a lower risk of Alzheimer's in comparison to someone who has never married, even again.
• 38:22
  Dr. David Perlmutter: That explains the statement, it is better to have loved and lost than never to have loved at all.
• 38:29
  Dr. David Perlmutter: Because you're targeting.
• 38:31
  Dr. David Perlmutter: Yeah, that's what I think.
• 38:32
  Dr. David Perlmutter: You're targeting your microglial cells with oxytocin.
• 38:35
  Dr. David Perlmutter: Every time you're with another person, you hug another person, you express your love, your gratitude, you're amplifying oxytocin.
• 38:41
  Dr. David Perlmutter: Your microglia are just so smiling and happy and want to do good things.
• 38:47
  Dr. David Perlmutter: Think about that.
• 38:48
  Dr. David Perlmutter: So a lot has been explained through this seeing the brain, at least, and the brain's destiny through the lens of these microglial cells over which each of us has great control.
• 39:02
  Dr. Jill Carnahan, MD: Yes.
• 39:03
  Dr. Jill Carnahan, MD: Is it any wonder?
• 39:04
  Dr. Jill Carnahan, MD: I mean, back in the medical School days, we had the objective hard science and then the woo stuff, which in my mind was human connection and hope and love and those things.
• 39:12
  Dr. Jill Carnahan, MD: But we're finding that woo stuff may be the most powerful medicine that we as physicians can give to patients, is sitting with them, being with them, hearing them, hugging them with permission, all of those things.
• 39:24
  Dr. Jill Carnahan, MD: Actually, I've found for my 20 plus years, like I said, those are powerful healers and yet I think they're underestimated.
• 39:30
  Dr. Jill Carnahan, MD: And now we finally know the science behind even us as physicians and connecting to our patients and the power of the healing.
• 39:38
  Dr. Jill Carnahan, MD: This is so good.
• 39:39
  Dr. Jill Carnahan, MD: I want to ask a few more.
• 39:40
  Dr. Jill Carnahan, MD: Rapid fire Jerry, you got.
• 39:42
  Dr. David Perlmutter: I know the rapid fire drill.
• 39:43
  Dr. David Perlmutter: These are worth twice as much.
• 39:45
  Dr. Jill Carnahan, MD: I know, right?
• 39:45
  Dr. David Perlmutter: Double value points, right?
• 39:47
  Dr. Jill Carnahan, MD: It's like a game show.
• 39:48
  Dr. Jill Carnahan, MD: The first one is, I'm sure there's an extensive list in your book of recommended labs.
• 39:53
  Dr. Jill Carnahan, MD: But if someone were to just say, what's the top five or eight or what are the core things that I should measure or ask my doctor for?
• 39:59
  Dr. Jill Carnahan, MD: What would you say for the key labs that are crucial?
• 40:01
  Dr. David Perlmutter: We have some exotic labs that are brain dedicated, like P Tau217, GFAP, neurofilament light.
• 40:09
  Dr. David Perlmutter: You know, many of your viewers maybe haven't heard of those, but they'll read the book, they'll understand what they mean.
• 40:14
  Dr. David Perlmutter: But the simple things that are critically important for brain health are your fasting blood sugar, if you can even take it to the extent of wearing a CGM continuous glucose monitor from time to time.
• 40:25
  Dr. David Perlmutter: That's really helpful to get a sense of the dynamics of your blood sugar.
• 40:29
  Dr. David Perlmutter: Fasting insulin, who gets that?
• 40:32
  Dr. David Perlmutter: Everyone should.
• 40:32
  Dr. David Perlmutter: When you get your fasting blood sugar, have them check your fasting insulin.
• 40:35
  Dr. David Perlmutter: You'll explain why Even your hemoglobin A1C, good to look at your inflammatory markers like C reactive protein, vitamin B12 level and homocysteine, really important vitamin D level as well.
• 40:50
  Dr. Jill Carnahan, MD: What are the top three supplements that you think really do have evidence or protective for the brain?
• 40:55
  Dr. David Perlmutter: Great question.
• 40:56
  Dr. David Perlmutter: I would say vitamin D often underrated, but we know that countless studies have demonstrated a relationship between higher levels of vitamin D and lowered risk of dementia.
• 41:10
  Dr. David Perlmutter: So vitamin D is critically important.
• 41:13
  Dr. David Perlmutter: I'm a very big fan of the Omega 3s, especially DHA.
• 41:18
  Dr. David Perlmutter: And you know, I think the B vitamins are underrated, especially for people who have elevated homocysteine.
• 41:25
  Dr. David Perlmutter: Doesn't get talked about a lot, but it's really important.
• 41:28
  Dr. David Perlmutter: That might be, you know, 20 to 25% of people who Have a little genetic issue whereby their homocysteine levels are going to be elevated.
• 41:37
  Dr. David Perlmutter: That genetic issue.
• 41:39
  Dr. David Perlmutter: Perhaps some of your viewers have heard of it, called mthfr.
• 41:43
  Dr. David Perlmutter: I have it.
• 41:44
  Dr. David Perlmutter: My homocysteine was elevated and taking methylated B vitamins has been the home run for me to get my homocysteine down to a level of about eight.
• 41:54
  Dr. David Perlmutter: So those are really.
• 41:55
  Dr. David Perlmutter: Well, I say they're the top three.
• 41:57
  Dr. David Perlmutter: They're among the list of the top supplements that come to mind right now.
• 42:02
  Dr. Jill Carnahan, MD: Fabulous.
• 42:02
  Dr. Jill Carnahan, MD: Couldn't agree more.
• 42:03
  Dr. Jill Carnahan, MD: And again, it's simple.
• 42:04
  Dr. Jill Carnahan, MD: It's not these complicated, super expensive things.
• 42:06
  Dr. Jill Carnahan, MD: We can start with the basics.
• 42:08
  Dr. Jill Carnahan, MD: Exercise.
• 42:08
  Dr. Jill Carnahan, MD: There's been a lot out there.
• 42:09
  Dr. Jill Carnahan, MD: Strength.
• 42:10
  Dr. David Perlmutter: Oh my gosh.
• 42:11
  Dr. David Perlmutter: Yeah, we cover it.
• 42:13
  Dr. Jill Carnahan, MD: Yeah.
• 42:13
  Dr. Jill Carnahan, MD: What's the best evidence base?
• 42:14
  Dr. Jill Carnahan, MD: Is it still aerobic?
• 42:15
  Dr. Jill Carnahan, MD: Is there another.
• 42:16
  Dr. Jill Carnahan, MD: What's your.
• 42:17
  Dr. David Perlmutter: The.
• 42:18
  Dr. David Perlmutter: The best evidence has been the combination of both aerobic and strength training.
• 42:23
  Dr. David Perlmutter: Resistance type exercise.
• 42:24
  Dr. David Perlmutter: Why?
• 42:25
  Dr. David Perlmutter: Because aerobic exercise actually more so, targets metabolism.
• 42:29
  Dr. David Perlmutter: But when we exercise, I. E. Use muscles, we are creating various chemicals.
• 42:35
  Dr. David Perlmutter: The muscles are an endocrine gland creating chemicals that go elsewhere in the body including the brain, help regulate our metabolism, help keep our blood sugars in check.
• 42:44
  Dr. David Perlmutter: Amplify activation of AMP kinase such that we activate nitric oxide and we can have better blood supply, better insulin functionality.
• 42:53
  Dr. David Perlmutter: Ultimately, some of the chemicals, at least one called Interleukin 6, amplifies this amp kinase.
• 42:59
  Dr. David Perlmutter: We know that irisin is another of these myokines activated by muscle activity, makes its way to the brain to produce something called brain derived neurotrophic factor bdnf.
• 43:11
  Dr. David Perlmutter: That amplifies our ability to what, Grow new brain cells.
• 43:15
  Dr. David Perlmutter: Who's not going to want that?
• 43:16
  Dr. David Perlmutter: So we want to have aerobic exercise so that the muscles are spitting out these wonderful myokine chemicals.
• 43:23
  Dr. David Perlmutter: But we want to have lots of muscle mass such that we make more of these.
• 43:28
  Dr. David Perlmutter: It's the pharmacy.
• 43:30
  Dr. David Perlmutter: Your body's pharmacy is this is muscle.
• 43:33
  Dr. David Perlmutter: So strength training then is really very important.
• 43:35
  Dr. David Perlmutter: So everybody asks that question that you just asked, which is important, you know, which is more important.
• 43:40
  Dr. David Perlmutter: And the question is obviously both.
• 43:43
  Dr. David Perlmutter: But I had a third, actually third and fourth part.
• 43:46
  Dr. David Perlmutter: And the third part is that you really need to involve yourself in a flexibility program each and every day because if you're not flexible, you're going to hurt yourself.
• 43:56
  Dr. David Perlmutter: And if you hurt yourself, then you're exercise program comes to a screeching halt.
• 44:00
  Dr. David Perlmutter: That's bad for your brain.
• 44:02
  Dr. David Perlmutter: The second part is do something that challenges your balance because if you're not working on balance, you Increase your risk of falling and again, break a hip.
• 44:11
  Dr. David Perlmutter: You don't exercise for however long that's going to take for your recovery.
• 44:15
  Dr. David Perlmutter: So I think it's four parts.
• 44:17
  Dr. David Perlmutter: I think it's exercise, flexibility, strength training and aerobics.
• 44:20
  Dr. David Perlmutter: And interestingly, a study was published just yesterday and it was an evaluation looking at the UK Brain Biobank and looked at people age 80 or older who were called super movers.
• 44:34
  Dr. David Perlmutter: And these are people who, they did a walking test and they were in the top 9% of the speed that they would comfortably walk, I. E. They always walk fast.
• 44:43
  Dr. David Perlmutter: Yes.
• 44:44
  Dr. David Perlmutter: Like I did when I made rounds.
• 44:46
  Dr. David Perlmutter: Right.
• 44:46
  Dr. David Perlmutter: You always got to walk fast.
• 44:47
  Dr. David Perlmutter: Yes.
• 44:48
  Dr. David Perlmutter: Anyhow.
• 44:49
  Dr. David Perlmutter: But they found that those individuals, and I think it was 4,000 people that they, they studied, had a 50% reduction in the risk of dementia.
• 44:58
  Dr. Jill Carnahan, MD: Wow.
• 44:58
  Dr. David Perlmutter: Walk fast.
• 44:59
  Dr. David Perlmutter: I mean, if people don't take away anything more from our time together today.
• 45:04
  Dr. David Perlmutter: Two words, walk fast.
• 45:06
  Dr. Jill Carnahan, MD: I love that because I've been accused many times of being a fast walker.
• 45:10
  Dr. David Perlmutter: Yeah.
• 45:12
  Dr. Jill Carnahan, MD: Okay, last thing.
• 45:13
  Dr. Jill Carnahan, MD: Ketosis and coffee.
• 45:15
  Dr. Jill Carnahan, MD: Yay or nay?
• 45:16
  Dr. Jill Carnahan, MD: Any thoughts on ketosis or coffee?
• 45:18
  Dr. Jill Carnahan, MD: Both.
• 45:19
  Dr. David Perlmutter: So yay.
• 45:21
  Dr. David Perlmutter: Yay on the coffee.
• 45:22
  Dr. David Perlmutter: Yeah.
• 45:23
  Dr. David Perlmutter: You know, coffee is the number one source of polyphenols globally and we talked about epigenetics and how.
• 45:32
  Dr. David Perlmutter: We didn't mention how polyphenols positively influence epigenetics.
• 45:36
  Dr. David Perlmutter: So coffee gets a, a very big nod in the positive.
• 45:40
  Dr. David Perlmutter: And ketones.
• 45:41
  Dr. David Perlmutter: Absolutely.
• 45:42
  Dr. David Perlmutter: We're looking at some really wonderful new interventions aside from just, you know, hard on being on a ketogenic diet, you know, which means, you know, being very restrictive as it relates to your carbs and eating more fats.
• 45:57
  Dr. David Perlmutter: But other interventions, you know, that we can use in terms of supplements to being really aggressive in raising our levels of blood beta hydroxybutyrate.
• 46:08
  Dr. David Perlmutter: We know that's good for the brain, we know that's really good for powering our brain cells and certainly good for the epigenetic component as well.
• 46:14
  Dr. David Perlmutter: So yay on the ketone, more of a ketogenic diet and yay on the coffee.
• 46:21
  Dr. David Perlmutter: So, yeah, both get a positive nod.
• 46:24
  Dr. Jill Carnahan, MD: Fabulous.
• 46:24
  Dr. Jill Carnahan, MD: I couldn't agree more.
• 46:25
  Dr. Jill Carnahan, MD: Last thing is, for you personally, what's made the biggest impact on your brain health?
• 46:31
  Dr. David Perlmutter: You know, I'm going to go for the, and I do all the things, you know, I'm careful about my blood sugar and exercise and all the things.
• 46:40
  Dr. David Perlmutter: I'm going to go for the love part, the connection part.
• 46:46
  Dr. David Perlmutter: I, I just know that's been so powerfully important for my brain.
• 46:53
  Dr. David Perlmutter: So there you go.
• 46:54
  Dr. David Perlmutter: Yeah.
• 46:54
  Dr. David Perlmutter: What can I say?
• 46:56
  Dr. David Perlmutter: That's my belief and I'm sticking to it.
• 47:00
  Dr. Jill Carnahan, MD: Thank you for ending with that deep compassion and just the heartfeltness of that statement, because that's how you and I connected over dinner.
• 47:08
  Dr. Jill Carnahan, MD: Just talking about what's really mattering in life, how do we make a difference, how do we connect?
• 47:12
  Dr. Jill Carnahan, MD: And I really believe that the more physicians and a lot of people out there listening are physicians, that we really dive into that human connection, part of healing that we've been told, at least for my medical education, that's not scientific.
• 47:25
  Dr. Jill Carnahan, MD: It's maybe the most scientific thing we could do and the most powerful.
• 47:29
  Dr. David Perlmutter: I'll never forget that dinner because we didn't know each other that well, and in five minutes went deep and then we had a conversation for two hours and all the dinner thing happened around us and we didn't really.
• 47:45
  Dr. David Perlmutter: I don't know, were we rude?
• 47:47
  Dr. David Perlmutter: I don't know.
• 47:47
  Dr. David Perlmutter: But were just so focused on this conversation that the whole dinner just came and went.
• 47:52
  Dr. David Perlmutter: And I remember how.
• 47:55
  Dr. David Perlmutter: Just how good that felt, you know, it was really.
• 47:58
  Dr. David Perlmutter: So we raised a lot of the oxytocin and we did great biomicroglial cells.
• 48:02
  Dr. David Perlmutter: There you go.
• 48:02
  Dr. David Perlmutter: Yes.
• 48:03
  Dr. Jill Carnahan, MD: And we need more of that, right?
• 48:04
  Dr. Jill Carnahan, MD: We need more of that connection.
• 48:06
  Dr. Jill Carnahan, MD: So 100.
• 48:07
  Dr. Jill Carnahan, MD: Yes.
• 48:07
  Dr. Jill Carnahan, MD: We will end there.
• 48:08
  Dr. Jill Carnahan, MD: Thank you for the work.
• 48:10
  Dr. Jill Carnahan, MD: I mean, besides this book, you've done a lot of work in the world to change RV medicine, but this is going to be maybe the biggest game changer of your career, and I'm so grateful.
• 48:21
  Dr. David Perlmutter: Thank you for having me.
• 48:23
  Dr. David Perlmutter: Anytime.
• 48:23
  Dr. David Perlmutter: Get to Connect is always very special.
• 48:26
  Dr. David Perlmutter: So thanks again.
• 48:27
  Dr. Jill Carnahan, MD: Hey, guys.
• 48:27
  Dr. Jill Carnahan, MD: I hope you enjoyed this very special edition of resiliency radio with Dr. David Perlmutter as much as I did.
• 48:35
  Dr. Jill Carnahan, MD: I love his brilliance, his heart, and the way he's bringing Brain Defenders, his latest book, to change the way we view our brains and medicine.
• 48:43
  Dr. Jill Carnahan, MD: And really, most importantly, empowering us.
• 48:45
  Dr. Jill Carnahan, MD: So I hope you got a good takeaway tips from that interview.
• 48:49
  Dr. Jill Carnahan, MD: As you know, we're out with new episodes every single week.
• 48:52
  Dr. Jill Carnahan, MD: If you haven't yet liked or subscribed.
• 48:54
  Dr. Jill Carnahan, MD: We've now hit 1 million subscribers, and I couldn't be more excited.
• 48:58
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• 49:00
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• 49:05
  Dr. Jill Carnahan, MD: That also helps us out greatly.
• 49:06
  Dr. Jill Carnahan, MD: And I will see you again next week for another new episode of Resiliency Radio.