# Microglia, Metabolism & the Future of Brain Health | HOMe Podcast #005

An episode of [Health Optimization Medicine Podcast](https://invisiblenetwork.ai/podcast/1663974629), 8 Apr 2026, 59 min.

Audio: https://traffic.libsyn.com/secure/672d8edf-a640-45ce-ac61-cd5f898a7b27/HOMe_005-AUDIO.mp3?dest-id=3824325

In this episode of the Health Optimization Medicine Podcast, Dr. Scott Sherr is joined by renowned neurologist and bestselling author Dr. David Perlmutter to explore one of the most important breakthroughs in brain health — the role of microglia. Often overlooked, microglial cells are the brain's immune system and play a central role in determining whether the brain thrives or degenerates over time. Dr. Perlmutter explains how these cells can shift between protective (M2) and destructive (M1) states — and how this shift underlies neurodegenerative diseases like Alzheimer's, Parkinson's, and more. Most importantly, this episode highlights how everyday lifestyle choices — from diet and exercise to metabolic health — directly influence brain function and long-term cognitive resilience. Join us as we delve into: • What microglia are and why they control brain health • The difference between M1 (destructive) and M2 (protective) states • How metabolism shapes the brain's immune response • Why conditions like Alzheimer's are rooted in immune dysfunction • The connection between blood sugar, insulin, and brain degeneration This episode is for you if: • You want to protect your brain and prevent cognitive decline • You're interested in the science of Alzheimer's and neurodegeneration • You want actionable strategies to improve brain health • You're curious about the future of brain optimization and longevity You can also find this episode on… Youtube: https://youtu.be/EMrlchMOZKk Find more from Dr. David Perlmutter Website: https://www.drperlmutter.com Book: https://braindefenders.com LinkedIn: https://www.linkedin.com/in/david-perlmutter-md/ Instagram: https://www.instagram.com/davidperlmutter/ Facebook: https://www.facebook.com/DavidPerlmutterMd/ Find more from Health Optimization Medicine and Practice (HOMeHOPe): Website: https://homehope.org/ Instagram: https://www.instagram.com/homehopeorg/ Virtual Symposium 2026: https://homehope.org/homehope-virtual-symposium-2026 Use PODCAST10 to get 10% OFF your purchase of the Clinical Metabolomics Module at https://homehope.org/products/clinical-metabolomics Find more from Troscriptions Website: https://troscriptions.com/ Instagram: https://www.instagram.com/troscriptions/ Use POD10 to get 10% OFF your Troscriptions purchase at https://troscriptions.com/collections/our-products

## Transcript

[0:00] Welcome back to the Health Optimization Medicine podcast.
[0:03] My name is Dr. Scott Scher, and I'm one of your hosts, and today's episode is a
[0:08] fantastic one with Dr. David Perlmutter.
[0:11] I'll give you a quick bio.
[0:12] And David, before we get started, he's a board certified neurologist,
[0:15] six time New York Times bestselling author on the board of directors,
[0:19] and as a fellow of the American College of Nutrition and currently
[0:22] serves as a director of Neuroscience Research at Brent Therapeutics.
[0:26] He received his MD from the University of Ma Miami School of
[0:29] Medicine, where he is awarded the Leonard g Roundtree Research Award.
[0:32] He serves as a member of the editorial board of the Journal of
[0:35] Alzheimer's Disease and has published extensively in peer reviewed
[0:37] scientific journals, including Archives of Neurology, neurosurgery
[0:40] in the Journal of Applied Nutrition.
[0:42] He's also a frequent lecture at symposia sponsored by institutions
[0:45] such as the World Bank IMF.
[0:47] Columbia University, Scripps, New York University, Harvard and more.
[0:51] He has books in 32 languages.
[0:54] The Surprising Truth about Wheat, carbs and Sugar Brain Maker, the Grain Brain
[0:58] Cookbook, and the microbiome in the brain.
[1:00] And his newest book that's coming out in August, 2026 is called
[1:04] Brain Defenders, and that's what this conversation was all about.
[1:10] Dr. Perlmutter and I went deep into these particular types of cells
[1:15] that he focuses in on the book.
[1:17] In the book called Microglia.
[1:19] He talks about how these particular cells, the immune
[1:21] cells of the brain, are essential.
[1:24] And when they're in the wrong format, when they're in their M1 format,
[1:28] specifically, they destroy brain tissue over time, and they're the cause of brain
[1:34] neurogen, neurodegeneration, no matter what the final etiology or the final.
[1:39] Presentation or condition you have immune system dysregulation
[1:44] at the microglia level.
[1:45] So we go further.
[1:46] We talk about what that is and how that happens, and we talk about mitochondrial
[1:50] function and the shift from oxidative phosphorylation to glycolysis.
[1:54] We talk about why this is happening with insulin resistance and toxins in our
[1:57] environment and medications that people are taking toxins in our, in our food,
[2:02] and obviously sympathetic activation.
[2:04] Other aspects of mitochondrial stress.
[2:07] From there, we go in to talk about what can we do about this, right?
[2:11] And so Dr. Perlmutter has a great way of describing this in his book.
[2:14] Dietary Interventions, lifestyle Interventions.
[2:16] Of course, the basics.
[2:18] What are you going to eat?
[2:19] What are you not gonna be toxic with all the time?
[2:21] And then in, in addition to that, what went even further, we talked
[2:24] about advanced mitochondrial testing.
[2:27] Is there a utility?
[2:28] What's coming out?
[2:29] What kind of testing can be very helpful?
[2:31] Looking at optimal ranges versus normal ranges.
[2:33] That was a big part of this conversation at the end, which was so important.
[2:36] We talked about novel supplementation, things like lithium or creatine and others
[2:41] that are, can be so helpful for the brain.
[2:43] We, in addition at the end, talked about.
[2:46] Breakthrough technology and, and therapeutics, including things
[2:48] like GLP ones, mitochondrial transplants, even gamma rays to your
[2:53] brain, infrared light, and more.
[2:55] This is a power packed huge, hugely fun recording for me because I, I've
[3:02] been a fan of David's work for a long, long time, especially as it relates
[3:04] to hyperbaric therapy, which he's a pioneer for back 20 or 30 years ago.
[3:08] So without further ado, please enjoy this episode with Dr. David Perma Perlmutter.
[3:12] Please don't forget to get.
[3:13] A copy of his book or sign up for a pre-release copy of
[3:17] it@braindefenders.com and enjoy.
[3:20] See you.
[3:21] Dr. Scott Sherr: Dr. David Perlmutter.
[3:22] It's very nice to see you again.
[3:23] How are you?
[3:24] David Perlmutter: I am great, Scott.
[3:26] How, how are you doing?
[3:27] Dr. Scott Sherr: I heard you just first got off a, just a trip from Alaska.
[3:30] Sorry, from Antarctica.
[3:31] Right.
[3:31] David Perlmutter: And Artie and Artie die, as they say down there.
[3:34] Yeah, it was, it was breathtaking and I actually wrote a blog about it because.
[3:39] You know, it's an interesting situation, uh, down there that in 19, uh, in late
[3:43] 1950s, the entire planet came together and said, we're gonna work together and
[3:49] cooperate and not, uh, exploit Antarctica
[3:52] and do research.
[3:53] And what a model, you know, for what could be.
[3:57] And I was thinking about that down there when, uh, and when you come back and see
[4:02] how things are currently in the world.
[4:04] What a model for what could, you know, what pe, how people
[4:07] could get along and come together and work towards a common goal.
[4:10] So it was beyond, you know, of course the, the, the natural aspect
[4:14] of what you get to see when you're down there, which was breathtaking.
[4:17] Dr. Scott Sherr: That's amazing and for on so many levels.
[4:18] I mean, we used to talk about this with space, even though, you know, there was
[4:21] the space races initially, if we could just coordinate and collaborate what, you
[4:25] know, what the possibilities could be.
[4:27] So that's super cool.
[4:28] You got to see it in action, especially with some amazing
[4:30] nature throughout the time, I would
[4:32] David Perlmutter: Oh Yeah.
[4:32] it was great.
[4:33] And the good thing I went with a, uh, a exploration group called Quark,
[4:38] and they really allow you to get into the environment.
[4:42] So, you know, we got to do kayaking and stand up.
[4:45] Uh, we didn't just, uh, stand up, uh.
[4:46] Paddling, but that was available.
[4:48] Uh, and so that's really to be in a kayak and, and going around the
[4:52] icebergs and looking at the panino and
[4:55] the seals and whales, right by you.
[4:57] Oh my gosh.
[4:58] It was, it was really breathtaking.
[5:00] So there, there actually are, um, tours that will allow you not only walk on
[5:05] the land, which we did, we went the zodiacs and did some walking, uh, but,
[5:10] um, snorkeling as well in a dry suit.
[5:12] And I'm, I'm looking forward next time to being able to do that.
[5:15] I would really enjoy that.
[5:16] Dr. Scott Sherr: Well, I mean, talking about a good brain reset, right?
[5:20] I mean, that's what you're all about in your new book.
[5:22] All about the microglia specifically is a really cool topic and one that I've been
[5:27] diving into deeply actually in very, very many ways in my own clinical practice.
[5:31] So I'm excited to kind of dig it in.
[5:33] But I think, you know, before we get too far into the weeds, and I have a lot of
[5:36] questions for you, I think maybe defining some terms would be helpful for people.
[5:39] Because you know, like just like you, we dropped acid with you back in the past.
[5:43] Now we're, now we're going and optimizing these cells called the microglia.
[5:47] So maybe if you can give us a little bit of a
[5:49] David Perlmutter: Sure.
[5:49] Let me give you the, the short, uh, short list on the glossary.
[5:53] So.
[5:54] Let me, let me give a bit of a preface to that because, uh, so people know
[5:57] why we're doing what we're doing.
[5:59] You know, for decades we've pretty well focused as it relates to what makes a good
[6:03] brain go bad on the fact that the brain tends to accumulate some strange proteins.
[6:08] In the case of Alzheimer's and.
[6:09] Beta amyloid and, and Parkinson's, uh, alpha synuclein.
[6:13] But we've now come to a different understanding of just over the past
[6:17] couple of years that really fundamental across the board in all of the common
[6:22] neurodegenerate conditions, Alzheimer's, Parkinson's, hunting, it's MS really
[6:27] is a focus on what's going awry.
[6:30] With the brain's immune system, the brain's immune system.
[6:34] Here's the first term to define, is made up of cells called the microglial cells.
[6:38] So, uh, as you and I pursue our discussion today, we're gonna be focused on these
[6:43] cells, microglial cells, and again.
[6:45] These are part of the brain's innate immune system that are basically
[6:50] determining its destiny and the empowering part of Brain Defenders.
[6:55] The, the book I wrote is that our day-to-day choices influence
[7:00] whether those microglial cells are going to be supportive, uh,
[7:04] allowing us to grow new neurons, allowing us to build new synapses,
[7:07] shoring up the blood-brain barrier.
[7:09] We call that the M two microglia.
[7:12] Or we foster the development of the evil twin, the M1 microglial cell
[7:18] that destroys our neurons, gets rid of synapses and threatens the
[7:22] integrity of the blood-brain barrier.
[7:25] Whether the microglial cells are friend or foe depends on their metabolism,
[7:31] how they are utilizing glucose in the presence of oxygen to make energy a TP.
[7:38] And it turns out, and this is I think one of the most important
[7:40] points of my entire book.
[7:43] That the metabolism and therefore the function friend or foe of
[7:47] the brain's immune cells mirrors.
[7:50] Our body's metabolism.
[7:52] So what does that do?
[7:54] It brings into focus all of the things that you've been talking about for
[7:58] years, about keeping our metabolism in check, optimizing our body metabolism,
[8:04] our body weight, our glucose, our our levels, our insulin functionality,
[8:09] our blood lipids, our blood pressure.
[8:12] All of these things converge on many things throughout the
[8:15] body, but for our time today.
[8:17] Dr. Scott Sherr: Mm-hmm.
[8:18] David Perlmutter: Converges on whether these brain immune cells are gonna
[8:20] be, you know, charting, uh, our destiny in a good way or a bad way.
[8:25] And we now understand that things like Alzheimer's, for example, are far more
[8:31] involved, uh, in what's going on with these microglial cells than, than looking
[8:35] at this beta amyloid, which is the.
[8:37] Target of pharmaceutical development, which has abjectly failed, uh, science,
[8:43] uh, magazine or science tech, I think, uh, in 2020, called the discovery of the
[8:48] role of microglia in brain health as the number one discovery for the year of 2025.
[8:54] So,
[8:54] you know, what we're talking about today is absolutely right on the edge, and
[8:58] most importantly, incredibly empowering.
[9:01] Dr. Scott Sherr: I love that.
[9:02] And so it reminds me of your trip to Antarctica where you could chart a
[9:06] course when you'll die down there because there's ice and you'll get stuck in it.
[9:11] Or you can chart a course when there's actually free water and
[9:14] you can actually float through it.
[9:15] Right?
[9:15] And how you're charting that course is really related to how these microglia
[9:20] are being activated either in the M two or N one category, right?
[9:24] Um,
[9:25] David Perlmutter: right.
[9:25] And.
[9:26] You think about the early explorers, uh, in Antarctica, they didn't,
[9:30] they didn't know, they didn't have GPS, they didn't really have much
[9:32] ability to forecast the weather, and
[9:34] it was kind of a roll of the dice.
[9:36] That's where we've been in brain health.
[9:38] Until just recently, uh, it's pretty much the, the messaging was live your life,
[9:43] however you choose, eat whatever you want.
[9:45] And when you start to becoming co uh, becoming cognitive impaired for getting,
[9:50] you know, wifi codes, grandchildren's name, where you are,
[9:53] you know, all kinds of, all manner of cognitive dysfunction, there's gonna be
[9:57] some wonderful pharmaceutical fix for you.
[10:00] Well, I welcome the day, believe me, I welcome the day.
[10:03] But we aren't there yet.
[10:05] And yet there are so-called Alzheimer's drugs that don't work, uh, at, in any
[10:10] meaningful way that are potentially life-threatening and certainly,
[10:14] uh, very risky to take.
[10:16] Anyway, with about 23 to 28% of people taking these drugs,
[10:20] having brain hemorrhages,
[10:21] that's
[10:22] Dr. Scott Sherr: crazy.
[10:22] Yeah.
[10:22] David Perlmutter: Uh, and we can do better.
[10:24] You know, we can really emphasize not treating Alzheimer's.
[10:28] But preventing it in the first place, you know, that's the
[10:31] ultimate principle of wisdom.
[10:33] Uh, according to the,
[10:35] the, the yellow emperor that in the fourth century BC
[10:38] curing, uh, you know, preventing a disease before it has really reared its ugly head.
[10:43] We know that we can do that now, e even independent of whether you carry
[10:47] these so-called Alzheimer's genetic predisposition or not, there's so much we
[10:52] can do, and that's what we'll talk about.
[10:54] Dr. Scott Sherr: Yeah.
[10:55] I know in the end of your book, which we'll get to it later, you talk about
[10:58] some promising advanced therapeutics and pharmaceuticals and technologies
[11:01] and some things like mitochondrial transplant, which is super interesting.
[11:05] But the bulk of your book obviously is on the things that we can do every
[11:09] single day to optimize our brain health and, and one other term I thought might
[11:12] be helpful to, to define that you talk about early in the book is also and been.
[11:16] Alluding to it already, but maybe just to define what you mean by
[11:19] immuno metabolism, and there's also this sort of extension of this word,
[11:24] which might be helpful that I've been talking a lot about with recently and
[11:27] colleagues is Immunosenescence as well,
[11:29] David Perlmutter: So immuno metabolism is a, a, a con, a contraction of
[11:35] the terms immunity and metabolism,
[11:38] you know, both of which have been front and center in, uh, our, uh, scope of.
[11:42] Interest at, at, you know, for a long, long
[11:44] time.
[11:45] Turns out that they're intimately related.
[11:47] That the, that our metabolism and people understand what that means.
[11:51] Keeping our, our bodies in shape, basically keeping our
[11:54] blood sugars under control.
[11:55] The things I mentioned earlier,
[11:57] our metabolism.
[11:58] Profoundly moment to moment influences the set point of our immune systems.
[12:03] Whether our immune systems are doing their job or they're overacting,
[12:07] uh, in which case we are reacting even against our own tissues.
[12:10] We
[12:11] call that autoimmunity or underperforming, in which case we are then susceptible
[12:15] to not only infection, but also cancer.
[12:18] You know, immunity involves surveillance, looking at our bodies, scanning for
[12:23] cells that are, are inappropriate and then can replicate, but.
[12:27] I think before I get to combining immuno, uh, immunity and metabolism,
[12:33] recognize that we are now looking upon the immune system as having
[12:36] a, a much larger responsibility, especially as it relates to the
[12:40] brain.
[12:41] Yes, the immune system in the brain is there to go into action when we have a
[12:44] viral infection, bacterial infection, uh, whatever it may be, uh, even trauma,
[12:49] for example, the immune system is activated to help deal with the debris
[12:53] and help healing take place.
[12:55] That's kind of the classical view of the immune system, but.
[12:59] You know, I, I, I like the metaphor of the fireman or the
[13:03] fire person in the firehouse.
[13:04] Yeah.
[13:05] That person's in the firehouse waiting for something to happen, and then when
[13:09] there's an alarm bell off, the fireman goes to, to deal with the problem.
[13:14] But what is that person doing between bells?
[13:17] He or she is at the firehouse, making sure that all the equipment's
[13:21] working, shining up the fire
[13:23] engine, testing all the valves, making sure that things are working.
[13:25] In other words.
[13:26] Doing maintenance and upkeep, and that's what the immune system is really
[13:31] doing all the time in our brains.
[13:33] It is ensuring that our synapses are connecting appropriately,
[13:37] that we can grow new neurons.
[13:39] Who knew, uh, when we need
[13:41] Dr. Scott Sherr: Right.
[13:41] We didn't know that for a while.
[13:42] Yeah.
[13:43] David Perlmutter: fundamentally.
[13:44] Two other things that is keeping the blood brain barrier, which we really depend upon
[13:48] intact and keeping inflammation at bay.
[13:53] Inflammation is a really central mechanism in terms of what
[13:57] makes a good brain go bad.
[13:59] And here's where we marry that term, the immunity term to the metabolism term,
[14:05] to come up with this notion of immuno metabolism term that I really love
[14:09] because it's the center of my life right
[14:10] Dr. Scott Sherr: Mm-hmm.
[14:11] David Perlmutter: that is that the, the function of these immune cells.
[14:15] It is dictated by their metabolism.
[14:18] You know, we look at
[14:20] our biology textbook at the cell and the cell has within it these things called
[14:24] mitochondria, the powerhouse of the cell.
[14:27] That's in the best of situations when our immune cell in the brain,
[14:32] the microglia are doing their job.
[14:34] They're, uh, keeping the neurons intact and the synapses functioning and
[14:39] everybody's happy, cleaning up debris.
[14:41] Really very important.
[14:43] Uh, and it's dependent upon their mitochondria, supplying them with adequate
[14:48] amounts of energy so they can remain in what we call this M two configuration,
[14:54] the loving, nurturing microglia.
[14:56] Now.
[14:57] That microglial cell can shift to become the evil twin, the
[15:02] M1 evil twin microglial cell.
[15:04] And when it does so that is the cornerstone of every neurodegenerative
[15:09] condition that you can think of.
[15:12] And I wanna come back to that thought just a moment.
[15:14] But that is a shift that happens when these immune cells have their metabolism
[15:20] shift again, immuno metabolism.
[15:23] And there are metabolism shifts when they are confronted by, hmm,
[15:27] products that are produced by two high blood sugar, by inflammation, by the
[15:32] excessive free radicals, reactive oxygen
[15:34] species, uh, any manner of.
[15:37] Uh, damage, what we call damage associated molecular patterns or, or things that are
[15:41] created when there's damage in the brain, uh, or PS pathogen associated molecular
[15:46] patterns when there's an infection in the brain and stimulates the conversion
[15:50] from healthy cells, uh, supportive cells to being disruptive, most importantly.
[15:56] This metabolic shift going away, sort of turning its back on the wonderful gift
[16:02] of the mi uh, mitochondria to another form of energy production that won't be
[16:06] on the quiz, but is called glycolysis
[16:08] when that
[16:09] Dr. Scott Sherr: my quiz.
[16:10] David Perlmutter: Yeah.
[16:10] You know, the, the points remember, is that that characterizes the shift
[16:14] of these immune cells turning their backs on us, destroying the brain.
[16:18] But the important point is we can shift them back.
[16:22] Remember, uh, Scott, I, I mentioned earlier that the metabolism of these
[16:27] cells mirrors the metabolism of your
[16:30] body.
[16:31] So when we do things to improve our body's metabolism, the play in the brain is
[16:37] shifting those M1 destructive microglia back to being supportive, and you become
[16:43] the architect of your brain's destiny.
[16:46] Dr. Scott Sherr: Cool.
[16:47] Awesome.
[16:48] I think you said that so well, David, where it's the M1 state, you know,
[16:52] it's this destroyer state, as you call it, of the microglia that's causing
[16:55] all of our neurogenic conditions, and I think that is a base for everybody
[16:59] listening is like what I got out of your book when I was reading.
[17:01] It's like this is really the.
[17:02] The lowest common denominator.
[17:04] And then you took it even further, which is it's mitochondrial dysfunction,
[17:07] which as we know, I mean, I was looking at statistics recently, about
[17:10] 94% of US adults have some element of mitochondrial dysfunction as well.
[17:16] And one thing I, I just have a small question about the M1
[17:19] David Perlmutter: Metabolic dysfunction.
[17:20] Dr. Scott Sherr: metabolic dysfunction, which is really
[17:21] a correlation to mitochondrial
[17:23] David Perlmutter: Agreed, and I'm so glad you said that.
[17:25] That's absolutely perfect.
[17:26] Dr. Scott Sherr: Yeah.
[17:27] When I think about M1, the only thing I, I small like nuance, is there any
[17:31] utility in the short term for microglia cells, you know, the primary immune cells
[17:36] of our brain to go into that M1 state.
[17:40] Okay.
[17:40] And to,
[17:41] David Perlmutter: point.
[17:41] Just like we need inflammation, although
[17:43] it's always castigated, we need inflammation, uh, you
[17:47] know, to do certain things.
[17:48] We need the M1.
[17:49] A configuration or what we call phenotype of these microglial cells
[17:53] from time to time to help us, uh, in terms of the immediate response to
[17:58] an event.
[18:00] The problem is that when we have diabetes or we are significantly
[18:04] overweight, uh, or have other metabolic issues, they tend not to wanna go
[18:09] back to being supportive again.
[18:11] So yeah, you That's a very good point.
[18:13] There's a time and a place for all these.
[18:15] Functions to occur, but it's the shifting back then to being M two
[18:20] supportive that is compromised by the things over which we do have control.
[18:24] And now this explains why we see such an increased risk of, um, Alzheimer's,
[18:31] for example, in the type two diabetic.
[18:32] We've wondered about it before.
[18:34] We said, well, yeah, you know, maybe there's some pro-inflammatory activity
[18:37] from this glycation of our proteins, or
[18:40] the increased inflammation or the insulin resistance.
[18:43] Knowing that insulin in the brain does some other things aside from allow glucose
[18:47] to be used as a fuel in certain areas,
[18:50] uh, it acts as atrophic hormone,
[18:52] but it allows us to understand that this explains for, here's a great example.
[18:57] If you experience head trauma outta the blue.
[19:00] Riding your bike, somebody cuts you off and you have head trauma, your.
[19:05] Risk for a worse outcome is increased if you happen to have been a
[19:11] diabetic at the time of that event.
[19:14] Now, think about that.
[19:15] Why on earth would that be?
[19:16] Because now that you're diabetic, yeah, you're gonna shift your M two to M1.
[19:21] Uh, pH uh, phenotype of your microglia cells because you've been injured.
[19:24] But again, it's that shift back that you depend upon to regain your functionality.
[19:29] So your, uh, risk of morbidity, prolonged morbidity, more cognitive
[19:34] issues after the same event.
[19:36] Is greater because of this issue.
[19:39] And again, you know, as a neurologist, we've learned to really be very
[19:46] specific about how we approach specific problems like Alzheimer's
[19:50] being unique as it relates to other neurodegenerative conditions.
[19:55] We would never consider that we're going to approach Alzheimer's in the same
[19:59] way we approach Parkinson's in the same way we approach MS or Huntington's,
[20:03] uh, chorea, whatever it may be.
[20:05] But this is a new reality because it turns out that this shift of the microglial
[20:12] cells from M two to destructive M1 is the fundamental across all neurogenerative
[20:19] conditions, and that's a hard.
[20:22] Forgive the pun, pill to swallow,
[20:24] uh, for neurologists because, you know, we've been trained to learn
[20:28] these specific protocols about each individual neurodegenerative condition.
[20:34] Now we're being told hopefully, uh, that, you know, as a matter of fact,
[20:38] there's something way upstream of all the bad stuff that goes on that
[20:43] then defines each of these diseases.
[20:46] And as a matter of fact.
[20:48] The data and the research that paved the way for this was
[20:52] actually Parkinson's research.
[20:54] I talk about it in the
[20:54] book that took place in around 19 82, 19 83.
[20:59] Gimme a minute.
[21:00] It's an interesting story.
[21:01] Uh, there was a, a doctor, uh, Jay, uh, William Langston working
[21:06] in his office in Stanford.
[21:08] One morning, an attending physician, and the residents burst in his office.
[21:12] You gotta come down to the emergency room to see this patient.
[21:15] Because we don't know what to do.
[21:16] We don't know if we're gonna admit this guy to psych.
[21:18] We're gonna admit him to neurology.
[21:20] Uh, you know, as a resident, you
[21:22] don't want to admit patients if you don't have to.
[21:24] So
[21:24] we're, we're pushing him into
[21:25] psych 'cause it's obviously a psychiatric issue.
[21:28] So they go down to the ER and there's a patient there who is stuck like a statue
[21:32] with his arm sticking up in the sky.
[21:34] They had brought him in from the jail.
[21:37] No one knew what to do with him.
[21:38] They couldn't get his arm to go down.
[21:40] And Dr. Langston pondered it and really had never seen anything like it.
[21:44] And over the next few days, several more people came in and some of them were
[21:49] less, uh, afflicted and he examined them.
[21:52] And, and some of the, uh, presentations I give, I actually showed the video
[21:56] of this, of what it looked like.
[21:58] And for all the world, it looks like Parkinson's disease, but
[22:01] whoever heard of Parkinson's coming on, you know, in one day.
[22:04] Dr. Scott Sherr: Radically.
[22:04] Yeah.
[22:05] David Perlmutter: The, the, the interesting thing that United, all
[22:08] these experiences was they had all been doing IV heroin from the same source.
[22:13] It turns out it was a designer drug.
[22:15] It wasn't actually heroin.
[22:17] And this, uh, because there was a flaw in the production of this
[22:21] designer drug, it was contaminated with something called MPTP,
[22:24] which was a mito and is a mitochondrial toxin.
[22:28] And what Dr. Langston surmised was that damage to the mitochondria in a
[22:33] certain part of the brain affected it.
[22:36] Its ability to make dopamine,
[22:38] therefore Parkinson's.
[22:40] Parkinsonism manifested.
[22:42] He treated them with standard of Parkinson's care for their symptoms,
[22:46] and oddly enough, they improved.
[22:47] Well, not oddly enough it, it made sense now in retrospect.
[22:50] But here's the, the part that's so fascinating that really, uh, played a
[22:55] fundamental role in why I wrote this book, and that is several of the patients
[22:59] died, you know, 10 to 15 years later.
[23:02] And Dr. Langston still really interested in this, actually wrote
[23:06] a book about it, uh, about the, the story of the frozen attics.
[23:11] Um, he wrote, he examined their brains.
[23:13] And what did he find that yes, the area was depleted of dopamine producing cells,
[23:18] the area called the substantial nigra.
[23:21] But when he looked at it on the microscope, what he found, this
[23:24] is, uh, I think it's exciting.
[23:25] I hope your viewers find it exciting.
[23:27] He found that the microglial cells.
[23:31] Still active 13 years later, still activated in the M1
[23:36] configuration, gobbling up these neurons that make dopamine.
[23:40] Dr. Scott Sherr: Crazy.
[23:41] That's
[23:41] David Perlmutter: That's, that's basically indicating that this was a
[23:45] fire that was set and it hadn't gone out.
[23:47] It was still smoldering.
[23:49] Why is it important?
[23:50] Well, we talk about.
[23:53] The cytokine storm, for example, in COVID, where
[23:56] suddenly these, uh, microglial cells, uh, get shifted over to the M1 configuration
[24:02] and send out all these cytokines inflammation throughout the brain, and,
[24:06] you know, that's a tragic situation.
[24:08] Then patients recover, but about 20%.
[24:11] Don't fully recover and haven't recovered to this day.
[24:15] We call them.
[24:16] Uh, we characterize 'em as having long COVID and what's going on with them
[24:20] is quite similar to what Dr. Langston described back in 1983 that these
[24:26] microglial cells got shifted from being supportive to being destructive.
[24:30] Not a cytokine storm now, but a cytokine drizzle brought on by the
[24:36] continued activation of these cells.
[24:40] We see the same thing in Alzheimer's.
[24:42] We see the same thing in ms. We see the same thing in
[24:44] Huntington's and certainly see the same thing in Parkinson's that doesn't
[24:48] necessarily get induced by doing IV drugs, but can be induced by exposure
[24:52] to paraquat, uh, trichloroethylene, which is found in industrial
[24:56] cleaning products, uh, and even head.
[24:59] Uh, there's a, a wonderful book written about this by Dr. Ray Dorsey
[25:04] that really makes it clear that Parkinson's is a manmade disease and
[25:07] is a consequence of, of toxin exposure.
[25:10] So the mission is to look upstream.
[25:15] At the microglial cells, uh, as being, you know, the real entry
[25:18] point as to where all, you know, the downstream damage is taking place.
[25:23] Target those microglial cells with the various techniques
[25:26] I talk about in the book.
[25:27] And then, you know, we explored, as you mentioned, uh, what the future holds and
[25:32] how so much research now has shifted over to looking at, uh, what can we do from.
[25:38] An invasive, uh, and, you know, a technological approach, pharmaceutical
[25:42] approach, targeting microglial cells, putting them back to being supportive
[25:46] and, and really bringing an end, uh, to the progression in these devastating
[25:51] degenerative conditions like Parkinson's and as it relates to Parkinson's.
[25:55] Oddly enough, it's already been done,
[25:58] published in, uh, April, 2024
[26:01] Dr. Scott Sherr: yes.
[26:02] I saw this.
[26:02] Yeah.
[26:02] David Perlmutter: highly respected New England Journal of
[26:04] Medicine.
[26:05] What did they find?
[26:07] And I'm not in, I'm not, let's be clear, I'm not advocating, uh, all
[26:11] Parkinson's patients use this approach.
[26:14] Uh, I'll, uh, preface my statements with that.
[26:17] But, uh, a study of I think 130, uh, Parkinson's patients versus Control one
[26:22] year study evaluated these patients over the one year using what's called the
[26:26] unified Parkinson's Disease Rating Scale.
[26:30] That basically measures how well they're doing and, uh.
[26:34] What they did was half the group got a GLP one agonist drug like ozempic, but
[26:41] a different one that seems to penetrate into the brain a little bit better.
[26:45] And what happened to the group getting the GLP one agonist drug is that their
[26:51] Parkinson's disease was fully arrested.
[26:56] IE they weren't cured, but they made no, uh, progression.
[26:59] They did not worsen at all during that one year.
[27:03] In contrast to the control group, that as one would expect, got significantly
[27:07] worse over the one year period of time.
[27:09] Now again, let me be clear.
[27:11] I'm not saying this is ready for prime time.
[27:14] But what do the GLP one agonist drugs do?
[27:17] They specifically bind to our microglial cells?
[27:20] They specifically enhance mitochondrial function, and as everyone now
[27:25] knows, they improve body metabolism.
[27:29] It's why people are taking them to lose weight.
[27:31] And what were they originally designed for?
[27:33] To bring blood sugar under control as a treatment for diabetics.
[27:38] So again.
[27:39] I am, as you could see, animated about
[27:42] the result of that study.
[27:43] Uh, but I, I, I, I discussed it in the book again, not to say, you know,
[27:48] GLP one, agonists for one and all,
[27:50] but I am saying that this is pretty profound evidence that when we
[27:54] target metabolism and then as a consequence of targeting metabolism,
[28:00] we target our microglial cells.
[28:02] Good things can happen.
[28:03] Dr. Scott Sherr: Yeah.
[28:04] I love that.
[28:05] And I think a big part of your book talks about how to defend your brain
[28:09] and of course this is where you're kind of going with talking about GLP ones
[28:13] and some of the novel therapeutics and pharmacologics and things like that, which
[28:16] I do want to dance with you a little bit on as well, because that's like the fun,
[28:20] exciting, like, like you talked about this study, but as you all very well
[28:24] describe in the book and had you have for.
[28:27] Decades now is that a lot of this is based on foundations, um, and foundational
[28:33] biology and lifestyle and diet.
[28:34] And I know you talk a lot about it, but maybe you can just give a little bit of
[28:37] an overview here of, of what you found to be the biggest intervention so far
[28:42] from a diet, lifestyle perspective, and even some supplementation if you'd like.
[28:46] Specifically when it comes to the microglia.
[28:50] David Perlmutter: Well, let me contextualize that first of all, because
[28:52] we talked about risk for these diseases.
[28:55] I mean,
[28:55] you know, diabetes certainly is a powerful risk for having your brain decline,
[28:59] uh, or, uh, as I mentioned earlier, having a worse outcome from head trauma.
[29:02] You know, we
[29:02] live in a country where 30% of people age 65 and over are diabetic now, not.
[29:10] Having a little insulin resistance of pre-diabetic, that's, you know, being
[29:14] full on diabetic, which as I mentioned, may as much as fourfold increase your
[29:18] risk for becoming an Alzheimer's patient.
[29:21] And, you know, as it relates to, um, you know, being pre-diabetic, the number
[29:26] is is, you know, certainly much, uh,
[29:29] Dr. Scott Sherr: It is staggering.
[29:29] David Perlmutter: larger.
[29:30] It's a third of us adults, and the scary part about that metric is that
[29:35] about 90% of these people don't know it.
[29:38] So that's why we do podcasts like you are doing and we
[29:42] write the books that we write.
[29:44] 'cause people need to be aware that, you know, getting a fasting blood
[29:48] sugar every year is interesting.
[29:49] People kind of train for that.
[29:51] I know, uh, I have a friend who says I'm not drinking for
[29:53] a month before my blood work.
[29:54] I
[29:54] Dr. Scott Sherr: Yeah.
[29:54] Right,
[29:55] David Perlmutter: that doesn't tell you any, that's bad information,
[29:58] but, you know, we can do a lot better than fasting blood sugar each year.
[30:01] We, at the very least, if you're doing blood work every year,
[30:04] by all means at least check.
[30:05] Um.
[30:06] In your fasting insulin level.
[30:08] So, uh, we've really gotta do the very best we can to look.
[30:12] At these metabolic, uh, indices and realize that we're in, you know,
[30:17] there are a billion obese people, uh, on our planet and you know, we have,
[30:22] uh, in America right now, 40.3% of American adults is obese with extreme
[30:27] obesity being at about, maybe about 16% of adults in America right now.
[30:32] Think about, that's extreme obesity.
[30:34] So that sets the stage, uh, for us to then look at.
[30:39] Then what are those lifestyle interventions?
[30:40] And you've been talking about these things for years.
[30:43] my my mission here was to contextualize them in the context of brain health.
[30:49] And that takes a little work for people, um, to, to, you know, to
[30:53] realize that, well, what's going on in my body's going to affect my brain?
[30:56] I mean, you know, and it does.
[30:58] I mean, we have a one in nine American adults right now,
[31:03] over the age of 65 is demented.
[31:06] And I think it's fully preventable.
[31:09] So
[31:09] Dr. Scott Sherr: it one out of three?
[31:10] If you live to 85, I think you're gonna be demented too.
[31:12] So I think 50 50 now.
[31:15] David Perlmutter: Uh, so then what are the big inroads?
[31:17] And, uh, I think we've gotta get people moving.
[31:19] We've got to get exercise to happen.
[31:23] Uh, exercise is the fundamental for improving metabolism, improving certainly
[31:29] body weight, improving, uh, glucose.
[31:32] Levels, improving insulin functionality, reducing inflammation, and secondarily
[31:38] through the effects of muscle activation on creating chemicals
[31:43] called myokines that are good for metabolism and good for the brain.
[31:49] So, uh, you know, WW we don't really consider our muscles
[31:52] to be endocrine glands.
[31:53] You ask people, what are your endocrine glands?
[31:56] Uh, these are things like, you know, the, the pituitary, the adrenal glands.
[32:00] These are glands that secrete chemicals that have an effect elsewhere in the body.
[32:04] Well, guess what?
[32:05] Your muscles are a powerful endocrine gland.
[32:08] The muscles are a wonderful pharmacy to create.
[32:13] Chemicals that go throughout the body, including the brain, and do great things.
[32:17] When we exercise, we trigger the brain to create BDNF brain derived
[32:23] neurotrophic factor that turns on the growth of new brain cells.
[32:27] Who wouldn't want that?
[32:29] That fosters.
[32:30] Microglial function to be in the M two configuration, and
[32:35] it helps us form new synapses.
[32:38] So, you know, the idea of exercising to activate our muscles, to create
[32:44] this array of chemicals like risin, Risin goes into the brain and.
[32:49] Turns on the production of BDNF
[32:51] interleukin six.
[32:52] We used to think, well that's a pro-inflammatory
[32:55] cytokine, that's a bad thing.
[32:56] No, when your muscles make interleukin six when you're exercising,
[33:02] that activates pathway for those who want to know what it is.
[33:06] The MP kinase, a MP kinase pathway
[33:08] that helps us with, uh, blood sugar regulation helps our bodies increase
[33:13] fat utilization as a caloric reservoir.
[33:18] So again.
[33:19] That's what our muscles do.
[33:20] It's why exercise is so darn important.
[33:23] The bigger our muscles, the more of those chemicals they're gonna produce.
[33:27] Yeah.
[33:27] Dr. Scott Sherr: Can you be too big though, David?
[33:29] Can you get too big?
[33:29] What do you
[33:30] David Perlmutter: Yeah, you can overdo anything as you well know,
[33:32] and I'm sure you've been through overdoing.
[33:34] I,
[33:34] I certainly have been through there, through that myself, still
[33:37] paying for it over the years.
[33:39] Uh, but that said, yeah, but I think, uh, you know, we, we tend
[33:43] to experience as we age something called sarcopenia, and that's a
[33:46] fancy term, meaning that we lose muscle mass.
[33:48] And I, I really think that, uh, this is first and foremost.
[33:53] In terms of our obligation to our metabolism and our
[33:56] obligation to our brains, and that is to not lose muscle mass.
[34:01] How do we do that?
[34:02] We do it with a combination of aerobic training, strength
[34:05] training, or resistance training.
[34:07] Uh, and also, um, I think, uh, stretching and balance training
[34:12] are very important as well.
[34:13] I say that.
[34:14] Why?
[34:15] Because if you're, if you don't stretch.
[34:17] You're gonna injure yourself.
[34:19] And if you injure yourself, then you stop exercising.
[34:20] And if you don't work on your balance training as you get older, uh,
[34:24] which deteriorates as we age, you're gonna fall or you might fall, sorry.
[34:28] And if you do, again, you get injured and then you stop
[34:31] exercising and you can't afford
[34:33] that.
[34:33] If you do, uh, exercise is your key to reducing your risk for Alzheimer's.
[34:38] It's that simple.
[34:39] It's also your key to reducing your rate of cognitive decline.
[34:44] It also is your key to increasing the size.
[34:48] Of your brain's memory center called the Hippocampus.
[34:52] Uh, that was, uh, done, that was researched from a, uh, dr, uh, Kirk,
[34:56] uh, at the University of Pennsylvania, who was really first to show the
[35:00] powerful effects, uh, using, uh, MRI imaging after one year of intervention
[35:06] of people stretching versus people involved in an active exercise
[35:09] program, and actually demonstrated an increase in size in the exercise
[35:14] group versus the stretching group.
[35:16] Of the hippocampus in the hippocampus, uh, size deterioration, uh, was seen
[35:21] in the group that did not, uh, exercise actively, but did the stretching.
[35:26] And they also demonstrated improved memory simply with the intervention of exercise.
[35:31] So, you know, uh, the book talks about these incredibly cool new supplements
[35:37] that are targeting the microglia.
[35:39] exercise is
[35:39] key.
[35:40] Uh.
[35:41] Would say that whatever diet works for you to keep your blood
[35:44] sugar under control, that's good,
[35:46] needs to be fiber rich to nurture microbiome.
[35:49] Polyphenol rich means a lot of color.
[35:52] Uh, and, you know, look at what are the sources of polyphenols, uh,
[35:56] in your diet right now, the most common source of polyphenols in
[36:01] the human diet globally is coffee.
[36:04] So there you go.
[36:05] That's, that's a vote in favor.
[36:07] That's a bit self-serving, uh, for me 'cause I love my coffee.
[36:11] But again, colorful, polyphenol rich foods are really what we need to gravitate to.
[36:16] So, uh, you know, and I think we, we've got to be looking at those metrics that
[36:20] tell us how well we are doing from a, um.
[36:23] A metabolic
[36:23] perspective, not just what is our fasting blood sugar?
[36:26] What is our fasting insulin levels?
[36:27] Should be around two, maybe three.
[36:29] Our A1C should be around, you know, 5.2, 5.4.
[36:33] You see all uh, ads on television for diabetes drugs saying, I'm so
[36:37] happy I got my A1C below seven.
[36:40] That's not good In anyone's book,
[36:44] brain begins to deteriorate at A1C of 5.8.
[36:48] What is it telling us?
[36:50] Telling us we're already on the scale for insulin resistance.
[36:53] We're paving the, the road for getting us to being a full on diabetic.
[36:58] As I mentioned before,
[37:00] that's a surefire way of converting your, uh, microglial cells, your M two
[37:05] brain defenders that want you to have a healthy brain to turning their backs
[37:09] on you and becoming M1 the evil twin.
[37:12] That's what nurturing our brain defenders is all about.
[37:16] Now, I I wanna just.
[37:18] Throw at your viewers, a couple of supplements they may not have heard of
[37:21] that we mentioned in the book, and then
[37:22] we'll talk about some, some that have, um, certainly been talked about before.
[37:27] Uh, first, uh, well first I wanna mention what I think might well
[37:30] be one of the most important supplements, and that is, uh, creatine,
[37:34] Dr. Scott Sherr: Mm-hmm.
[37:35] I was gonna ask you about that.
[37:36] David Perlmutter: creatine, monohydrate, or, uh, creatine, a hydrochloride.
[37:40] We're seeing some, um, interesting data coming out, uh, indicating that.
[37:45] There may be some benefits of choosing creatine hydrochloride,
[37:48] uh, but nonetheless, uh, creatine is a wonderful way to, um, help our
[37:53] mitochondria do what they want to do.
[37:56] In other words, mitochondrial function, metabolic function,
[37:59] keep the microglia supportive.
[38:01] And that said, uh, it's pretty much a tasteless supplement.
[38:05] I, for one, don't know anyone who's not tolerated creatine.
[38:09] Uh, it's very inexpensive.
[38:11] Uh, and I. Don't want to point fingers, but I don't see an anyone
[38:15] having an excuse not to take creatine.
[38:17] Uh, I have no financial interest, uh, uh, currently in any creatine product.
[38:22] Dr. Scott Sherr: There's a lot out there too.
[38:23] Yeah.
[38:23] David Perlmutter: Uh, and I think a minimum dosage would
[38:26] be five grams twice a day,
[38:29] Dr. Scott Sherr: Twice daily.
[38:30] Okay.
[38:31] David Perlmutter: interventional trial actually looking at individuals.
[38:34] Who did have, um, existing low grade, uh, Alzheimer's disease.
[38:39] The, the trial used 10 grams twice a day.
[38:43] There really were no issues, uh, that were related to, um, uh,
[38:47] to taking that, that supplement.
[38:49] So really, very, very important Now.
[38:52] Oftentimes overlooked issue that relates to increasing inflammation
[38:57] and free radical stress in the brain, and therefore, targets our brain.
[39:02] Defenders is elevation of something that may, maybe your viewers have not heard of,
[39:07] but some of them have called homocysteine.
[39:11] It'd be great if you put a graphic on the bottom right now.
[39:13] It's really important, homo.
[39:15] Why?
[39:16] Because.
[39:18] Homocysteine is a, an amino acid basically that can accumulate, uh, and when it
[39:23] does, it becomes pro-inflammatory.
[39:26] It detracts from our body's ability to make something called glutathione,
[39:29] which we need as an antioxidant, as an anti-inflammatory, and to
[39:33] help us with detoxification and.
[39:36] Genetic testing can identify people who are at risk for having
[39:40] a higher homocysteine level.
[39:43] It's called the M-T-H-F-R Polymorphism.
[39:46] About 28% of Americans carry it.
[39:48] I carry it.
[39:49] And what is the fix for that?
[39:51] Whether you have that genetic thing or not?
[39:54] If your homocysteine is elevated, if it's around 11 or 12 or 10, needs to be around
[39:59] nine or even eight would be even better.
[40:02] Then you have to take a B complex.
[40:04] Simple enough.
[40:05] But importantly, it has to be what's called methylated.
[40:10] Be complex.
[40:10] You wanna drive that homocysteine level down, that's cool for the brain.
[40:15] Your brain's gonna love that.
[40:17] Your brain is threatened by a higher homocysteine level.
[40:20] High homocysteine is associated with an increased risk for Alzheimer's
[40:24] as well as cardiovascular disease.
[40:25] So, um.
[40:27] We can tease apart what should be in that B complex.
[40:29] But, uh, as you know, it's going to have B six methylated folene,
[40:33] uh, might even have some B two riboflavin, uh, trimethylglycine.
[40:37] We certainly also want to have adequate amounts of magnesium on board and zinc.
[40:42] Uh, you know, you will
[40:44] get those in a, any multivitamin.
[40:48] Um, but these, all, these all conspire to help bring your homocysteine level
[40:51] down.
[40:52] And after about three months, you wanna recheck that some.
[40:55] Of my patients have actually needed, uh, self-administered,
[40:59] they learn to do it at home.
[41:00] Subcutaneous injections of methylated B12, not a big deal.
[41:05] You know, once a week you could, people, you know, learn how to give
[41:08] themselves, uh, peptides For right now, you know how many people, what 20% of
[41:13] American adults, it's given themselves an injection with a GLP one drug.
[41:17] So you could
[41:17] sure learn how to give, uh, methylcobalamin.
[41:21] Uh, or, uh, yeah, a B12 injection, 5,000 micrograms a week.
[41:26] But follow that homocysteine level.
[41:28] Um, there are a couple of other, uh, interesting.
[41:31] Dr. Scott Sherr: Yeah.
[41:31] I was gonna ask you specifically about Lithium, 'cause I know you mentioned
[41:34] it in your book if, if you have any
[41:35] David Perlmutter: I, you know, I, I did mention lithium.
[41:37] Uh, lithium has been, uh, found to be suspect of interest as
[41:42] of late in, in the brain world.
[41:44] We know that, uh, lithium, uh, may well, uh, be something a go-to.
[41:49] It's a drug.
[41:50] Although there are supplements available,
[41:52] Dr. Scott Sherr: Yeah.
[41:52] Lithium carbonate.
[41:53] Yeah, lithium
[41:53] David Perlmutter: you can buy online or wherever a health food store.
[41:57] Uh, but there is an indication that this is really, uh, important for, uh,
[42:01] the way that it shifts the microglial
[42:04] cells, lithium, and all the good things that it does targets the microglial
[42:09] cells and helps to shift them, uh, from being, uh, M1 back to being or keeping
[42:14] them in their M two configuration.
[42:16] So I, when I first wrote the book.
[42:20] You know, that was already about a year ago.
[42:23] I, I will admit that, uh, when I finished that section on Lithium, the
[42:27] language was, we're gonna need to wait for more research until, uh, you know,
[42:31] I'm, I'm full on endorsing lithium.
[42:33] But over the period of time while we were writing and editing, more research
[42:38] came out that really was supportive.
[42:39] So as you saw the, uh, the language I used, I am supportive.
[42:43] Dr. Scott Sherr: Yeah.
[42:43] And, and that there's so many other supplements that I, that,
[42:46] that you talk about in the book.
[42:47] You do a great job.
[42:48] But one of other aspects I wanted to kind of cover, uh, are the,
[42:51] is the testing side of things.
[42:52] And you talk about some of the new mitochondrial tests out there.
[42:55] Um, some of the other testing like the, the brain marker testing that you can do.
[42:59] How do you feel about those kinds of tests?
[43:02] I've, I've talked to clinicians.
[43:04] You know, myself included, we're not entirely convinced that the
[43:07] mitochondrial testing is ready for prime
[43:08] David Perlmutter: And I agree with you.
[43:09] Dr. Scott Sherr: so I'd love to hear your perspective if you want to, uh,
[43:11] elaborate on that and maybe some of the other brain marker testing like
[43:14] PTA and others that you're thinking about using in the context of all this.
[43:19] David Perlmutter: Well, let's first talk about mitochondrial testing and, uh,
[43:22] there is a, a scan, uh, a test called me.
[43:26] Screen,
[43:27] uh, that I'm looking at.
[43:29] And, uh, I've had countless conversations with their development team.
[43:34] I think they've reached the point that it really does have validity.
[43:37] Uh, is it the end all?
[43:39] The end all.
[43:39] The gold standard is a muscle biopsy.
[43:41] Needle biopsy.
[43:43] Dr. Scott Sherr: Not easy for people to do.
[43:44] David Perlmutter: The various stages of mitochondrial function,
[43:47] of electron transfer and, and also the byproducts of mitochondrial
[43:51] function versus dysfunction.
[43:53] Uh, I, I like this test though, and I, I think they've done a great job.
[43:58] They are validated at several, uh, academic institutions,
[44:01] so.
[44:01] I'm on board,
[44:03] uh, with them and, and the, the thing that really convinced me
[44:06] was, you know, they're, they're beginning to demonstrate changes
[44:09] in their results with intervention.
[44:11] That's really where,
[44:12] Dr. Scott Sherr: That was my next question.
[44:13] David Perlmutter: goes.
[44:13] Um.
[44:15] But I would say that before we get to anything too sophisticated, like
[44:18] p tal two 17 and the various beta amyloid markers and um, uh, you know,
[44:24] neurofilament light, et cetera, the things we talk about in the book, you
[44:27] know, those might be a little bit, uh, too sophisticated for people and I get
[44:31] it, and I, and, uh, but it is available and I put the resources where people
[44:35] can get these, uh, um, tests performed.
[44:38] But I think that we're gonna, the big bites, uh, you know, are gonna occur.
[44:42] The broad strokes.
[44:44] By simply looking at the very simple metrics of, uh, metabolism.
[44:48] And I think
[44:49] one of the most fundamental tests that you can get that is really difficult
[44:53] to perform and requires that you buy something, uh, it's called, um, a tape
[44:59] measure that you put around your waist.
[45:01] And I, you know, it's funny, I, because the way I, I, I parsed that out, but,
[45:05] Dr. Scott Sherr: I love it.
[45:07] David Perlmutter: it's huge.
[45:08] I mean, you know, the waist to hip.
[45:10] Ratio tells us an awful lot about metabolism and therefore mitochondrial
[45:15] function.
[45:16] Dr. Scott Sherr: Mm-hmm.
[45:17] David Perlmutter: So, you know, we, we are pretty well, you know, Sy anonymize.
[45:21] Is that a word?
[45:22] I don't know.
[45:22] Uh, mitochondrial function with metabolism, because
[45:25] they go hand in hand as
[45:26] Dr. Scott Sherr: They do.
[45:26] David Perlmutter: function declines.
[45:27] So our metabolism declines and vice versa.
[45:30] Again, getting us back to the term immuno metabolism.
[45:33] Metabolism.
[45:34] So, you know, this is very simple.
[45:36] Fasting blood sugar is important.
[45:37] More important, better would be looking at, um, continuous glucose
[45:42] monitoring that gives you such a. More granular, in depth understanding of
[45:48] what your personal, uh, blood sugar dynamics are doing during the course
[45:53] of your day based upon your lifestyle choices, your current body habitus,
[45:59] and absolutely your genetics as well.
[46:01] And frankly, that's what you should be caring about, not how my fasting blood
[46:06] sugar each each year compares to what is
[46:10] considered
[46:10] Dr. Scott Sherr: for it too, right?
[46:11] David Perlmutter: or in the normal range.
[46:13] I can't.
[46:14] I have a tough time with that term
[46:16] as the hair goes up in the back of my neck when people say,
[46:18] yeah, I'm in the normal range.
[46:20] Yeah, you wanna be in the optimal range.
[46:22] If we're working together, we're gonna be going for the home run here.
[46:26] You know, we don't want to be a average.
[46:29] That's what in the normal range is.
[46:31] You know, you sample 10,000 people and you develop a bell curve and
[46:35] you want to be within, you know, one or two standard deviations of
[46:38] the mean and ain't good enough.
[46:41] Not at all.
[46:41] And we're not gonna, not gonna let you go there.
[46:43] We're gonna say, look, we want your fasting blood sugars maybe
[46:46] in the mid to upper eighties.
[46:48] Whoa.
[46:48] But my doctor, my doctor said, no.
[46:51] Let's look at the, look at the scientific literature and not try
[46:54] to keep you in what the lab reports as being in the, in the norm range.
[46:57] We talked about already a fasting insulin and you know, this notion of
[47:01] having an A1C below seven that is a. That is, uh, you know, a false goal.
[47:08] We, we can
[47:08] do absolutely much better than that.
[47:10] Dr. Scott Sherr: When you, when you think of, I, I have a couple
[47:12] of just final questions, but one on optimal ranges, which I'm a huge,
[47:15] huge proponent of this, well, you don't wanna be normal for your age.
[47:18] You wanna be optimal.
[47:19] Is there a way you define this for people specifically, or how
[47:22] do you create your optimal ranges?
[47:24] David Perlmutter: are out there.
[47:25] When you look at the research that, you know, brain Defenders is, is full
[47:28] of, I, I describe why it is I say this,
[47:33] where those changes, those inflection points begin in the laboratory testing.
[47:38] So I defend.
[47:39] You know, the idea that I have different, uh, laboratory measurement recommendations
[47:44] compared to, uh, in the normal range.
[47:47] So, um, you know, I, I think labs are gonna say anything below 11 on your
[47:51] homocysteine is in the normal range.
[47:54] That's, um, I'll be nice.
[47:56] That's,
[47:57] not good enough for your
[47:59] patience for anyone I'm interfacing with and for readers of my
[48:02] book, we want to do better.
[48:04] Look, you know, um.
[48:06] We have 6 million Alzheimer's patients now in America with that
[48:09] number going to double by 2050.
[48:12] And there is no meaningful treatment.
[48:15] So, um, it's, it's all about prevention and these are the
[48:20] keys to the kingdom.
[48:21] This, so you're not at the doctor's office saying, you know, I'm not
[48:24] remembering why I go into a room.
[48:27] Uh, and because that's the harbinger to, uh, issues down the
[48:31] road that are, are gonna present themselves sooner than later.
[48:35] So, uh, and at which at point we are told that what you do is, well, then
[48:40] you get into some, either a clinical trial or you go ahead and take a
[48:43] drug that's targeting beta amyloid.
[48:46] It doesn't work.
[48:47] I wish it did, if it did.
[48:50] I would have recommended it for people, including my own father.
[48:53] And, you know, I'd love there to be a drug and,
[48:56] you know, frankly, uh, lithium, uh, is, has been used as a drug,
[49:01] uh, for an awful long time, and there may be some play there.
[49:05] I even discuss in the book as, as you know.
[49:08] The idea that if the research on GLP one agonists, the ozempic like
[49:13] drugs in Alzheimer's and other neurogenic conditions demonstrates
[49:17] efficacy and safety, uh, long term, uh, then I, I will be supportive.
[49:23] You bet.
[49:24] So, you know, it's a notion of, of not alternative medicine that says
[49:29] either A or B, it's integrative medicine, which means I'm gonna take
[49:33] a look at A, B, C, and D. Uh, and value their risk benefit, uh, ratio to
[49:39] determine what I think is best for you.
[49:42] Dr. Scott Sherr: I love it.
[49:42] And you talk, one thing on the optimal range is that I, that we do, so we have a
[49:46] nonprofit that helps train practitioners.
[49:48] We talk about an, an optimal range, somewhere between 21 and 30 years of age.
[49:52] So that's when you're the most optimal, typically, when you have the most optimal
[49:56] levels of hormones and nutrients and things like that to be the most resilient.
[49:59] So that's what we try to, to teach.
[50:00] And, and that's exactly what you're saying, which is that you don't
[50:03] wanna be normal for your age at all.
[50:05] And I just wanted to kind of kinda relay that back to you.
[50:07] And, and, and the other aspect of it, 'cause I know that we're
[50:10] running outta time, is you were talking about some of these new, you
[50:13] know, promising pharmaceuticals and breakthrough breakthrough therapies
[50:16] and you talked about GLP ones, and I think that's, that's a great one.
[50:18] Are there any other ones that you'd like to highlight, you know, as we
[50:21] kind of finish up today about some, like, things that you're really
[50:24] excited for in the future as well?
[50:26] David Perlmutter: Yeah.
[50:27] And, and, and let me just say, 'cause you, you brought up an interesting point
[50:29] about saying that, you know, people in their twenties and thirties, that's
[50:32] what we should look at in terms of determining what an optimal might be.
[50:36] Perhaps in terms of, of hormones, but maybe
[50:39] not.
[50:40] Uh, but we recognize that, you know, the seeds are sown for Alzheimer's.
[50:46] For example, in our twenties and thirties.
[50:47] Those metabolic, uh, precursors begin in those years.
[50:52] So word only true that people in their twenties and thirties are
[50:56] metabolically intact these days 'cause
[50:58] they're not.
[50:59] Dr. Scott Sherr: I know.
[50:59] It's a good point.
[51:00] David Perlmutter: it, it, we have to take a step back and look at and
[51:02] help redefine what optimal may be
[51:04] and, uh, how we do that.
[51:07] Uh, I think it's a little bit unclear, but I think it's to look at the literature
[51:10] and see where people really push these labs and what the outcomes
[51:14] are when people have a fasting blood sugar of X, whatever it may be.
[51:19] So in closing, uh, you asked the question, well, what am I really excited about?
[51:24] A lot, I have to say.
[51:26] Uh, the future looks bright.
[51:28] Uh, there's one technology that really thrills me, and it's called,
[51:32] uh, it, it targets something in the brain called gamma oscillation.
[51:35] Dr. Scott Sherr: I was reading.
[51:35] Yeah.
[51:36] David Perlmutter: There's a beautiful sinus.
[51:38] Soil means up and down like the waves at the beach.
[51:41] Uh, background activity in the brain that is called gamma oscillation.
[51:47] you look at that background, smooth oscillation, it's much
[51:51] deteriorated in virtually all neurodegenerative conditions.
[51:55] If you
[51:55] look at that background oscillation in the Alzheimer's
[51:58] patient, it's all over the place.
[51:59] And, and you know, the symphony is not lined up.
[52:02] There's no conductor, the instruments are playing.
[52:05] Uh, but there, you know, it's cacophony basically.
[52:08] So, uh, forward thinking researchers, uh, especially a Dr. Leeway, si and
[52:13] I, I quote her work in the book.
[52:16] I asked the question, how can we reestablish the gamma oscillation in
[52:20] the brains of Alzheimer's patients and might that have some clinical benefit,
[52:25] bring the conductor back on board.
[52:27] And her mission was to find some technology that could do that with
[52:32] the idea that she would target.
[52:35] Guess what?
[52:36] The microglial
[52:37] cells and bring them back online.
[52:39] Uh, bringing back our brain defenders, uh, and helping, you
[52:42] know, get away from that evil twin.
[52:44] And she found, uh, in laboratory rodents that if she were to flash a
[52:51] light in front of these rodents in their eyes, uh, at various frequencies,
[52:55] things would happen in the brain.
[52:57] And she found that.
[52:59] Uh, a certain frequency of light, uh, would restore gamma oscillation.
[53:03] Wow.
[53:05] They then said, well, you know, it's an innocuous sort of intervention.
[53:08] Let's try it in humans, and found that shining a light at 40 times per second,
[53:13] flashing at a rate of 40 times per second, coupled with sound at 40 hertz as well,
[53:19] reverted the brains back to gamma oscillation restored,
[53:23] brought the conductor on board
[53:25] and.
[53:26] Then she said, well, you know that what we've got to do is, uh, we've gotta try
[53:31] this in patients with early Alzheimer's.
[53:33] And really across the board, she demonstrated improvement, uh, uh,
[53:38] in comparison to people not treated, uh, or a decline in their rate, uh,
[53:43] reduction, their rate of cognitive decline as it relates to memory.
[53:46] And importantly, and, and excitingly she demonstrated.
[53:50] Doing, uh, what are called volumetric, MRI scan, basically showing how much brain is
[53:56] there in a really significant, uh, slowing of the, the rate of brain loss in
[54:01] Alzheimer's patients by shining a light in their eyes and having them listen to
[54:06] a sound with a pair of headphones, uh, for, you know, a period of an hour a day.
[54:11] Far more impressive results than we've ever seen with any drug
[54:15] that's already FDA approved.
[54:17] So, you know, I guess in closing, um, that's one of the most exciting,
[54:23] uh, technologies I think that is on, is on the near, uh, horizon line.
[54:28] Uh, and there are other things, you know, real powerful intervention.
[54:31] You mentioned beginning of our time together, mitochondrial transplant
[54:34] and even, uh, technologies using small molecules to target certain receptors.
[54:41] On the, uh, microglial cells to revert them back to being M two supportive
[54:46] brain defending microglial cells.
[54:48] And a report that was published a couple months ago doing
[54:52] microglial transplants in humans.
[54:55] Dr. Scott Sherr: Wow.
[54:55] Really.
[54:56] David Perlmutter: Yeah.
[54:56] So this is, it's the future.
[54:58] It is the present.
[54:59] Uh, I think in closing, I just wanna say that.
[55:03] Each and every one of your viewers now has powerful tools to reign in their
[55:08] microglia and revert them back to being supportive and really, uh, become the
[55:12] architect of their brain's destiny.
[55:15] Dr. Scott Sherr: Well, well thank you David.
[55:16] That's amazing.
[55:17] And you know, the last question I'll ask you is your daily non-negotiables for
[55:21] optimizing your health and your microglia.
[55:23] Are there things that you absolutely will do no matter where you are in the world?
[55:26] 'cause I know you travel, you're in Antarctica, you're in other places
[55:29] around the world, traveling and speaking.
[55:30] What are some of your non-negotiables no matter what you are, where
[55:33] you are and what you're doing?
[55:36] David Perlmutter: I, I, I don't know that this targets my microglia.
[55:39] I think it does, and through some mechanism that I'll mention in a moment.
[55:43] But I think the non-negotiable for me every day is expressing gratitude.
[55:47] Dr. Scott Sherr: Mm, mm-hmm.
[55:48] David Perlmutter: you know, I could finagle a way to
[55:49] tie that into my microglia.
[55:50] Dr. Scott Sherr: Parasympathetic activation
[55:52] David Perlmutter: You bet,
[55:52] Dr. Scott Sherr: you know.
[55:53] David Perlmutter: reduction of cortisol,
[55:54] helping my HRV
[55:56] Dr. Scott Sherr: Yeah.
[55:57] David Perlmutter: helping me, then with all kinds of things
[55:59] like better sleep, uh, more dedication, dedication to exercise, um, you
[56:04] know, I exercise every single day.
[56:07] Are there days?
[56:08] That traveling just makes it, uh, you know, absolutely impossible.
[56:12] You're on a 12 hour flight.
[56:13] It's, it's challenging, but
[56:14] I, you know, even on the plane, I get up and look really goofy at times, walking
[56:18] up and back, you know, I don't want to get a dv, deep vein thrombosis, all that.
[56:22] But,
[56:22] Dr. Scott Sherr: Yeah.
[56:23] Yeah, sure.
[56:23] David Perlmutter: I exercise, you know, every single day.
[56:26] Just got some new equipment in my gym.
[56:28] Dr. Scott Sherr: Nice.
[56:28] David Perlmutter: Uh, that's I think really helpful.
[56:30] Uh, I've never been a stationary bike.
[56:32] Uh, user.
[56:33] I now have one that's so high tech.
[56:35] It's great.
[56:36] I get to gamify my stationary bike time.
[56:38] So I, I really, um, I, that's really important.
[56:41] Diets, you know, for the past 30 years has been,
[56:45] you know, something I've really focused on, but exercise is
[56:47] really key and, and I'm grateful.
[56:48] I'm a good sleeper.
[56:49] So do I have room to improve?
[56:51] You bet.
[56:51] I do.
[56:52] And are there new supplements every week that people are,
[56:55] you know, emailing me about and
[56:56] showing me data?
[56:57] You bet there are.
[56:58] And it can only take so, so many.
[57:00] But I think we covered.
[57:02] Some of the most important ones and certainly, those lifestyle
[57:05] factors that are really important.
[57:07] Dr. Scott Sherr: Yeah.
[57:08] Well, I just wanna thank you for all your pioneering work for so many years, David.
[57:11] People like me have been watching and listening and going to your lectures
[57:14] for, you know, as long as I've felt like I've had a brain that's been adult sized.
[57:19] So I just wanna thank you for all that.
[57:20] And just, I guess lastly, let let it let people know about your book when it's
[57:23] coming out, and how they can get it.
[57:26] David Perlmutter: Brain defenders.com.
[57:28] Oddly enough, that's the website, brain defenders.com, and here's
[57:31] what the cover looks like.
[57:32] Look how proud I am.
[57:33] Brain Defenders,
[57:34] uh, this book is published in August of, uh, this year, 2026.
[57:40] Presales are available right now, but I think if people go to brain defenders.com,
[57:44] they can learn what the book is all about.
[57:47] Read the endorsements.
[57:48] Uh.
[57:49] For whatever reason, we've already sold this book, uh,
[57:52] to 15 languages, 15 countries.
[57:55] So, um, I think it's gonna be a, a game changer for at least, you know, our
[58:00] understanding that we gotta move away from this idea of, if we can get rid of
[58:04] beta amyloid in your brain, problem solved
[58:06] Dr. Scott Sherr: Let's leave
[58:07] David Perlmutter: you know, basically, uh, putting the ball back on our side
[58:10] of the court that we have to make better decisions so we don't have to
[58:13] be thinking about an Alzheimer's drug for ourselves and our loved ones.
[58:19] Dr. Scott Sherr: Well, you have a great rest of your day.
[58:20] David.
[58:20] Thank you so much for all of your work and please everybody check it
[58:23] out brain defenders.com and have I wish you a great rest of your
[58:26] David Perlmutter: Thank you, Scott.
[58:26] It's so great to see you.
[58:28] Dr. Scott Sherr: Likewise.

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