192: Dr. Perlmutter: How to Protect Your Brain From Alzheimer's & Cognitive Decline

What if your risk of Alzheimer's isn't predetermined by your genes—but influenced by the metabolic health of your brain? My guest, Dr. David Perlmutter, is a board-certified neurologist, six-time New York Times bestselling author, and one of the world's leading voices on brain health and neurodegenerative disease. His latest work reveals a fascinating shift in how we understand Alzheimer's and Parkinson's: the role of the brain's own immune cells. At the center of our conversation are microglia—specialized immune cells that can either protect your neurons or contribute to inflammation and neurodegeneration. Dr. Perlmutter explains why their function is closely connected to metabolic health, and how insulin resistance, obesity, poor sleep, gut dysfunction, chronic inflammation, and environmental toxins may influence the way your brain ages. We also challenge the idea that carrying APOE4 means Alzheimer's is inevitable and examine research showing how lifestyle interventions can influence cognitive function—even later in life. In this episode, you'll learn: • How microglia can shift from "brain defenders" to drivers of neuroinflammation • Why metabolic health and insulin resistance are connected to Alzheimer's risk • How the gut microbiome, leaky gut, antibiotics, and inflammation can affect the brain • What emerging research says about GLP-1 drugs for Alzheimer's and Parkinson's • Why current amyloid-targeting Alzheimer's drugs may not address the underlying problem • How sleep, exercise, nutrition, and environmental exposures can influence cognitive aging We also explore emerging approaches to brain health, including 40 Hz light and sound therapy, TREM2, mitochondrial health, and metabolic monitoring. The biggest takeaway for me is that protecting your brain starts long before memory loss appears. Your genetics matter—but so do your metabolism, sleep, exercise, environment, and the choices you make every day. You have more influence over how your brain ages than you may think. Learn more about Dr. Shah: Website: drshah.com https://drshah.com Clinic: next-health.com https://www.next-health.com Instagram: @extend_podcast and @darshanshahmd Learn more about Dr. David Perlmutter: Website: drperlmutter.com https://drperlmutter.com/ Dr. Perlmutter's groundbreaking new book, Brain Defenders, is now available. Discover how to protect your brain and future health - order today at braindefenders.com https://www.braindefenders.com Thank You to Our Sponsors: Next Health Longevity Summit: Head to next-health.com/summit https://www.next-health.com/summit to secure your spot at the first ever Next Health Longevity Summit in Nashville on September 12th! Timeline: Timeline powered by Mitopure just dropped the price. Check it out using link shop.timeline.com/DRDARSHANSHAH https://shop.timeline.com/DRDARSHANSHAH for up to 20% off when you subscribe and save. IM8: Try IM8 today with a 30-day money back guarantee. Get 10% off your first order with code DRSHAH at im8health.com/drshah https://im8health.com/drshah

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Dr. Darshan Shah?

  Before we get started with this episode, I'd like to invite all of you to the first ever Next Health Longevity Summit, happening in Nashville, Tennessee, at the Conrad Hotel on Saturday, September 12, 2026. This is an all-day summit where you're going to be hearing from some of the best speakers in longevity's medicine, including Dr. Vanda Wright, Dr. Luisa Nicola, many of the podcast guests that you've heard here on the Extend Podcast, and of course, I'm going to be there, curating the entire day. We also have incredible vendors coming, so you can try the latest technologies in health, wellness, and longevity. Go to next-health.com/summit and buy your ticket today. We only have 400 spots and they're

• 0:40Dr. Darshan Shah?

  going quickly. That's next-health.com/summit. I look forward to seeing you all there.

• 0:50Dr. Darshan Shah?

  Welcome to Extend with me, Dr. Darshan Shah, a podcast dedicated to cutting-edge science, research, tools, and protocols designed to help you extend your health span. Having become one of the youngest doctors in the country at the age of 21, and trained and board-certified at the Mayo Clinic, I've accumulated three decades of practice as a board-certified surgeon and longevity expert. Over that time, I've discovered that a mere 20% of health knowledge yields 80% of the results when it comes to your health span. We are living in a new era where we are creating a new healthcare system, no longer focused on disease management, but achieving optimal health and vitality. Join me as I interview world-renowned experts, offering you a step-by-step guide to proactively avoid disease, and most importantly, extend your health span.

• 1:37Dr. Darshan Shah?

  Dr. Perlmutter, it's an incredible honor to have you back on the Extend Podcast. Thank you for doing this.

• 1:41Speaker 01

  I feel great in this seat. It's so good to see you as well, Darshan.

• 1:44Dr. Darshan Shah?

  Yeah, we added a table. Did you notice that?

• 1:45Speaker 01

  Uh, I can't say that I necessarily remember that, but I, that's what, I'll go with it.

• 1:51Dr. Darshan Shah?

  You've probably done like a couple of podcasts since then, but in a few studios, just like two or three.

• 1:55Speaker 01

  Yeah, I have my, and do mine as well. So it's a great experience, though. You get to talk to really interesting people and go wherever you want in the conversation. Life is good.

• 2:05Dr. Darshan Shah?

  I would say it's my favorite thing I do.

• 2:07Speaker 01

  Yeah, I agree. I agree. Cause you'll learn. You learn a lot.

• 2:09Dr. Darshan Shah?

  I learn so much and, you know, we rarely get a time to have focused conversations with people that last an hour long, and it's just fantastic. I love it.

• 2:16Speaker 01

  That's true.

• 2:17Dr. Darshan Shah?

  I know. Well, here we are with a paradigm-shifting book, and I would say like when we really need it, around neurodegenerative disease. So I'm so excited to talk about brain defenders with you.

• 2:29Speaker 01

  As am I. Who knew?

• 2:32Dr. Darshan Shah?

  And I mean, I think you probably knew for a long time. It seems like, reading through your books, you, you've kind of been leading up to this one all, the whole time.

• 2:41Speaker 01

  That's exactly right. I didn't know that.

• 2:43Dr. Darshan Shah?

  Yeah.

• 2:43Speaker 01

  I didn't know that that's what this would represent for me. I mean, we'll talk about what it represents for the reader.

• 2:48Dr. Darshan Shah?

  Right.

• 2:49Speaker 01

  But for me, it's the coalescence of really everything I've talked about, whether it's the, we didn't have the term ultra-processed foods back in the Grain Brain days. It was, you know, highly-processed carbohydrates, or the microbiome that I talked about in Brain Maker. But all of these ideas that were so important at the time, now seen through the lens of the brain's immune system.

• 3:10Dr. Darshan Shah?

  Right.

• 3:11Speaker 01

  Everything now makes total sense.

• 3:13Dr. Darshan Shah?

  Yeah, I completely agree with you is, you know, you are fighting this massive wave against you. Just keep pushing. I just imagine you on a beach getting pushed back by the traditionalists that focusing on the amyloid theory.

• 3:30Speaker 01

  Well.

• 3:30Dr. Darshan Shah?

  And you just kept fighting forward with this.

• 3:32Speaker 01

  Yeah. And you know, we'll get, we'll definitely unpack the amyloid theory, but the metaphor there is, you know, there, and when you look at martial arts, for example, Japanese martial arts, when you're struck, it's always a hard block. It's a, it's a confrontational block.

• 3:48Dr. Darshan Shah?

  Right.

• 3:49Speaker 01

  Whereas a lot of the Chinese art forms just deflect and move on. And I, I tend to feel like what we're doing is deflecting and letting them go their way with a, put a smile on your face, you know, have your, you know, talk about beta amyloid all you want, but the science is rising to the top now. And, and I think logic and compassion is prevailing, which we've needed for a long time. This idea that beta amyloid is the cause of Alzheimer's is really, it was always, you know, a hypothesis, the amyloid hypothesis. It doesn't work. It's not serving anybody. It's leading to the development of drugs that are hurting people and not helping people. So do I object to it? You bet I do. But, you know, we're gonna, we're gonna look at the glass being half-full.

• 4:31Dr. Darshan Shah?

  Exactly. Yeah, I love that. And so I think that brings up kind of a overarching concept here, which is the smoke versus the fire, right? Is that a good place to start here?

• 4:40Speaker 01

  You, we'll start wherever you want, but I love that. That's great.

• 4:43Dr. Darshan Shah?

  So let's, let's talk about that. What is the smoke with Alzheimer's and neurodegenerative disease versus the fire?

• 4:48Speaker 01

  Great question. And the smoke is, are, the smoke is the symptoms that we deal with. Let, in Alzheimer's, it's the cognitive decline. That's the smoke. That's not what is causing the problem. In Parkinson's, when we think about the smoke, we're thinking of tremor and rigidity and gait dysfunction and constipation. Who knew there was a GI component? But the fire is the underlying metabolic issues that affect the brains, the brain's immune system. These cells, the immune cells of the brain, what's going wrong is their metabolism is being challenged. Hence, we have a new term called immunometabolism. Immuno deals with the immune system, metabolism, how they're making energy. And this is fundamental,

• 5:30Speaker 01

  not just to Alzheimer's or Parkinson's, but all neurodegenerative conditions. Can you imagine? We're having a conversation today that all neurodegenerative conditions are predicated on this one upstream event, which is the shift of the brain's immune cells away from being supportive brain defenders to being destructive. And the most empowering part of this discussion will be how we can make that happen. And we can reestablish their metabolic health and allow them to shift back to being supportive.

• 6:02Dr. Darshan Shah?

  Yeah, it's, it just goes all the way back to, you know, Dr. Bland's writings and everything that you've been talking about, about the root causes. Like, if you just go back down to why all of this is happening, whether it be neurodegenerative disease, cardiovascular disease, even autoimmune disease, there's this connection between the immune system and a metabolism that's always been there. But because we're so siloed in medicine, we tried to think of diabetes as completely separate from immune issues, completely separate from brain issues. And, you know, you're a neurologist and kind of, you've lived, you lived in that world for so long that we just separate everything, but they're all connected.

• 6:40Speaker 01

  It's true. I mean, it's looking at the bigger picture. Actually, Dr. Bland just wrote a piece, I don't know if he's published it yet, that really looks at this whole notion of looking at the body, you know, through the lens of, of a network, that everything is interrelated. You know, when I wrote about the gut-brain connection, you know, back in 2016, you know, people were saying, well, what are you talking about? The gut? How in the world can that influence the brain? You know, now it's, it's self-evident, of course. And everybody's talking about the gut-brain connection, why you should take this probiotic or eat this food, whatever it may be, because it has a play in terms of what's going on in the brain. Most importantly, how the gut influences the brain's immune system, and then the role that that plays. You know, we tend to think of the immune

• 7:24Speaker 01

  system in the brain and in the, and people, first of all, they're very surprised that the brain even has an immune system. But we think of immune responses, what do we do when we're confronted by a pathogen, a virus, a bacterium, you know, a cancer cell, whatever it may be. But the reality is that we've now looked upon the immune system as doing a lot of maintenance work as well, a lot of day-to-day upkeep, that when there's no fire, the guys are back in the, in the firehouse, cleaning and making sure that the fire truck's going to work really well. It's only when there's an event or a challenge that the immune system then comes into play. That's old school.

• 8:03Dr. Darshan Shah?

  Yeah.

• 8:03Speaker 01

  The immune system is constantly, in your brain right now, tidying up, making sure that your neurons are working well, that your synapses are happy, your connection of one neuron to the next. And these microglial cells, the cells of the brain's immune system, are actually shoring up, hopefully, your blood-brain barrier. And immunometabolism, their metabolism dictates whether they're friend or foe, whether they're the good twin or the evil twin. We want them to be M2, the good twin, as much as we can. It all depends on their metabolism, how well and how effectively their mitochondria are working to make energy. And the take-home message is that the metabolism of these cells in your brain mirror your

• 8:48Speaker 01

  body metabolism. And that is hugely empowering, because you control your body metabolism. Everything you do, your exercise, your diet, your sleep, are all levers to impact your body metabolism and mirroring in your microglial cells, determining your brain's destiny. You're the architect.

• 9:06Dr. Darshan Shah?

  So what you're saying essentially is that your brain's immune system has a metabolism, and just as well as our body's metabolic system is functioning, our brain's metabolic system will mirror that. So it's a one-for-one connection. If we have good physical metabolic health in our body, as you know, we talk about this with continuous glucose monitors and fasting insulin level, so too will follow our brain's immune system.

• 9:31Speaker 01

  Exactly right. And it finally then explains, when you get what you just said so eloquently, when you get that, then you have an aha moment, because now I get why type 2 diabetes is associated with a threefold increased risk of Alzheimer's. Why I get the relationship of midlife obesity to Alzheimer's risk and hypertension to Alzheimer's risk, because these are metabolic challenges reflected in the brain's immune cells. They're either going to be brain defenders, or when they're metabolically challenged, they shift and they become our worst enemy. And we can alter our lifestyles now to keep them in their supportive M2 configuration, and we could help morph them back to being in that configuration

• 10:14Speaker 01

  based on our interventions. That's what we describe, and that's what we need to be doing.

• 10:19Dr. Darshan Shah?

  So why do they shift into this state where they're net harmful to us? What is evolutionarily happening there that they actually even have that mode to begin with?

• 10:29Speaker 01

  Well, there's an upside to that mode in the acute sense. In an acute infection, or acute trauma, or even a stroke, we want to activate these microglial cells in a time when we are suddenly having compromised mitochondrial function, which is severe. Compromised mitochondrial function, metabolic function is what characterizes this shift away from being supportive to being now destructive. But we want to have that activity take place in a very measured, short-term reaction to a threat. It's the limitation of that that needs to be targeted. So when we're metabolically challenged to begin with, when we're diabetic and have a head injury, our outcome is worse than if you're not diabetic at the front end. So that's the message here.

• 11:14Speaker 01

  Things are going to happen to us, right? We're going to get bumped on the head. We're going to have infections of one sort or another. How the brain deals with it, those cells will shift, but they need to be able to shift back. If other straws exist on the camel's back, they won't shift back. They will continue to increase their production of inflammation. What does that do? Inflammation from any source in the body, from the gut, wherever it comes from, even from the microglial cells themselves, further changes the good microglia into being destructive. So that creates a feed-forward process that will spread through the brain, and it explains a lot. You know, we've wondered in this chronic traumatic encephalopathy, football players get bumped in the head,

• 11:58Speaker 01

  they stop playing football, but they continue to decline. Why? Because their microglia have become activated and they don't shift back. So it spreads to the brain like a cancer. We can target these microglial cells now. I mean, we'll talk about the lifestyle issues, the interventions that you're doing already. But to call it like it is, there's amazing technology being explored, transplanting healthy microglia into the human brain, transplanting mitochondria into the human brain, as well as novel therapeutics in the realm of pharmaceuticals that are being now explored, and even cross-purposing existing pharmaceuticals

• 12:38Speaker 01

  that have been shown through pathways that you're aware of, like metformin, for example, GLP-1 agonist drugs that target metabolism. Therefore, let's take a look at this as it relates to our toolbox.

• 12:52Dr. Darshan Shah?

  Oh, so not only do we have lifestyle changes, but we also have existing drugs and technology and future ones that could potentially be shifting these microglial cells back into a protective state versus a harmful state.

• 13:07Speaker 01

  What you just said means the future looks bright.

• 13:09Dr. Darshan Shah?

  The future looks really bright on this, and things you can do right now, too.

• 13:13Speaker 01

  That's right.

• 13:13Dr. Darshan Shah?

  I think there's this overarching kind of dread in people that once you have a family history of Alzheimer's or Parkinson's, that you're probably going to be at high risk for it, too. And there's nothing you can really do about it, but the reality is the opposite.

• 13:28Speaker 01

  Yeah, and it's funny because on the way over here, there was some questions that I had to review to answer for some publication. That was the first question, not the answer to the first question. The first question was, what is the biggest myth that you want to dispel as it relates to Alzheimer's disease? And it was that question that you just posed. And that is that, my father died of Alzheimer's, and you know, that said, it's not in the cards for me. Why? Because I'm playing the hand. I am the architect of my brain's destiny. So that's the biggest thing I want to really rewrite for people. You know, many people know their family history and/or

• 14:13Speaker 01

  have done their three X four genetics, or whatever their genetic panel is, and know that they carry the APOE for allele, either one or two copies, and have been told that this is not a good thing, that you're in deep trouble, you're likely going to get Alzheimer's. And let's make it very clear, nothing is further from the truth. Again, you are the architect of your brain's destiny despite your genetics.

• 14:40Dr. Darshan Shah?

  Right, right. And I agree with you completely from everything I've read, everything I see. But you know, I was just at Stanford, I did a talk there, very optimistic about a lot of things around metabolic health. And someone asked me, is Alzheimer's disease preventable? And my answer was just same as yours, but there was a neurologist there from Stanford that said, you're only about 50% right. 50% of people that are going to get Alzheimer's are still going to get Alzheimer's. And this is a highly trained neurologist.

• 15:13Speaker 01

  I will take that. If I can reduce the risk of Alzheimer's by 50%, that is beyond a home run, beyond a grand slam home run.

• 15:22Dr. Darshan Shah?

  That's true, too.

• 15:22Speaker 01

  If we could reduce Alzheimer's by 20%, and I know that we can. I mean, in 2024, the Lancet Commission published their report showing that if we paid attention to 14 modifiable lifestyle factors, we could accomplish that. We could reduce Alzheimer's by as much as 50%. And that's a disease affecting 7 million Americans, costing us $360 billion a year, 55 million people globally. And that number is predicted to triple by 2050. That's what, 24 years away from now? So this by any stretch is an epidemic, if not a pandemic, it's global. By every definition, this is a pandemic.

• 16:03Speaker 01

  And the increase in Alzheimer's is in lockstep with the increase in our metabolic issues, in lockstep with obesity trends and diabetes trends. So if it were a genetic issue, then the incidence wouldn't be increasing with them. Our genes are not changing. The outflow of our genes is changing. So the outflow is based on the information our genes are receiving from our environment, including the foods that we are eating, the things to which we are exposed. So we are changing our gene expression. Not the APOE4 allele that you may or may not carry, or the pre-senilin 1, or now been identified, you know, more than a dozen significant gene risk factors,

• 16:48Speaker 01

  but they can be offset. That's the empowering part of the story here. Not, oh, I carry a particular genomic profile, and I'm basically doomed to get this, no matter what I do. No, I mean, the notion of live your life, come what may, and hope for the drug to fix it. I mean, James Cameron, the movie director, said that hope is not a strategy. Let's do a strategy here, based on science. So the Pointer Study that was published in JAMA last year, this was a study of 20,111 individuals, interventional trial, a two-year study. And they had two groups.

• 17:30Speaker 01

  The first group had 36 interventions over a two-year period of time, virtual and in real life, working with diet, working with lifestyle, working with exercise, stress management, et cetera. The other group, wouldn't call it a control group, but they were given the right diet and lifestyle choices, types of exercises they should do. They met with these people either two or three times a year. There wasn't really much interaction. And some of these people, across the board, they were metabolically compromised. They were elderly people, they were 68 years as average. Is that elderly? No, that's late middle age.

• 18:09Dr. Darshan Shah?

  I agree. Let's redefine elderly.

• 18:11Speaker 01

  Anyway, so these people across the board were expected to decline cognitively. That's what happens when you get to be my age. Well, they reevaluated them after two years, and what did they find? And these included people who carried the genetic risk factor called APOE4, right? 28% or so. And what they found was, with the aggressive intervention, they not only stabilized their cognitive function, they improved, including the APOE4 people who were told, you know, you're going to get, and you're already declining, you're in big trouble. The part of that story that I think is really interesting, it doesn't really get as much airtime,

• 18:53Speaker 01

  is the fact that the group that did not have the deep hand-holding, you know, they gave them the information to hope for the best, they improved as well.

• 19:03Dr. Darshan Shah?

  Oh, interesting.

• 19:04Speaker 01

  So it really speaks to the idea that empowerment through information is really going to move the needle. And that's what your life is all about, what you do.

• 19:14Dr. Darshan Shah?

  Absolutely, yeah. And I think, you know, that we live in a country right now where 7% of people are metabolically healthy. I mean, that's such a terrible number. And what I found has been moving the needle the most with people's metabolic health is just the information. And obviously, GLP-1 stacked on top of that has made a major change. But the information, I think, is still 80 to 90% of the change that we see.

• 19:41Speaker 01

  And upstream of all of that is, people have asked me in recent days, okay, Dr. Fulmer, what's the one thing? Everybody wants the one thing, I guess for TikToker, who knows?

• 19:52Dr. Darshan Shah?

  That's a TikTok one, right?

• 19:53Speaker 01

  What's the one thing on the top of your list you can recommend? And the one thing I would recommend, if people want to do one thing, it's shift the mindset to one of embracing the idea that I am the architect of my own brain's destiny. The other stuff isn't going to happen until, number one, domino falls. Then you say, okay, now how do I do it? Then we can talk about sleep and diet and exercise and reducing exposure to toxins in the environment, whatever it may be. But first, you have to shift the ball, you have to recognize the ball's in your court, and that the idea, again, of living your life, come what may, and hoping for the medical fix, that is not a good plan. It doesn't work.

• 20:36Speaker 01

  There's nothing for you right now. I am hopeful that there is a, you know, there'll be developments. We're seeing the recent research, what is underway right now. And I'm very hopeful because it is targeting immunometabolism. You brought up the idea of GLP-1s. They are vigorously being studied as it relates to brain diseases. And I think it's worth looking at because...

• 21:03Speaker 01

  You know, call it like it is, Alzheimer's is pretty much a uniformly fatal disease. It's now ranked as the number three cause of death in America. And so, you know, the idea that, well, we got to worry about the side effects of GLP-1s, I agree. We got to worry about the long-term side effects, point well taken. But when you're facing a lethal situation, let's at least consider it. And again, it gets to the idea that metabolism is at the heart. It's what changes the immune system to being destructive. And is that, that is what is at play across all neurodegenerative conditions.

• 21:43Speaker 01

  And I'm sitting here at this table, talking to you with that kind of nomenclature, that every player in the neurodegenerative space is upstream affected by this issue related to changes in the brain's immune system.

• 22:01Dr. Darshan Shah?

  Right, right.

• 22:02Speaker 01

  So, you know, in 2024, a study appeared in the New England Journal of Medicine. We respect that journal, right?

• 22:10Dr. Darshan Shah?

  Very much.

• 22:11Speaker 01

  That looked at 157 individuals with full-on Parkinson's disease. Evaluated them, how are you doing today, beginning of the study? Half the group gets a GLP-1 agonist drug and half the group gets a placebo for one year. After the one year, the group getting the placebo declined in their functionality, as one would expect, with a progressive neurodegenerative condition like Parkinson's. The group receiving the GLP-1 agonist drug stabilized, in fact, had a slight improvement.

• 22:41Dr. Darshan Shah?

  Wow.

• 22:42Speaker 01

  You say, wow, I agree with your sentiment.

• 22:45Dr. Darshan Shah?

  Incredible, right?

• 22:46Speaker 01

  It's, it, it takes your breath away.

• 22:48Dr. Darshan Shah?

  Yeah.

• 22:49Speaker 01

  The decline was completely arrested. That's, that gets back to your question. That's treating the fire.

• 22:55Dr. Darshan Shah?

  That's treating the fire, right?

• 22:56Speaker 01

  And not just the smoke. The smoke, again, the symptoms. The fire is the inflammation. It's what the word means, inflame.

• 23:04Dr. Darshan Shah?

  Yeah.

• 23:05Speaker 01

  It's the fire that's destroying the brain. And this brain becomes quiescent when metabolism is targeted.

• 23:12Dr. Darshan Shah?

  Yeah. I think just so for the readers to understand, if you don't do anything, waiting for a medication to come out, you will most likely get worse, right? So, like you said, with the placebo, with the GLP-1, people that have Alzheimer's that maintain the same lifestyle do not fix their metabolic health. They will get worse because these are progressive diseases. They don't just stop.

• 23:36Speaker 01

  If you don't do the work, you will get worse.

• 23:39Dr. Darshan Shah?

  Right, exactly.

• 23:39Speaker 01

  So even if you take the new beta-amyloid targeting drugs,

• 23:43Dr. Darshan Shah?

  Right.

• 23:43Speaker 01

  you're absolutely going to get worse just about as fast as the people who are not taking the drugs. The only advantage that people taking, not taking the drugs, and significant advantage is they're not, they don't have the risk profile now of taking these medications.

• 23:57Dr. Darshan Shah?

  Right.

• 23:57Speaker 01

  So, I think I sent this to you, the recent Cochrane analysis came out that looked at, okay, people are being given these drugs for Alzheimer's. And how effective are they? And how safe are they? This was, you know, looking at 20,342 individuals across 17 studies for 18 months per study. And it found that the drugs don't work, the word that they used was trivial in terms of their effectiveness. And in the face of significant risk, more than 20% of these people get brain hemorrhages and/or brain swelling. And it's, you know, an IV to every two weeks at a cost of $40,000 a year

• 24:42Speaker 01

  that Medicare is covering. And I, I actually had this discussion with the director of Medicare and Medicaid for the United States a couple of weeks ago. And for a drug that isn't, isn't effective.

• 24:56Dr. Darshan Shah?

  Yeah.

• 24:57Speaker 01

  And yet, you know, when you look at the study published by Rudolph Tanzi and Dean Ornish last year, an interventional study of 57 people, a small study, for 20 weeks. They said, we're going to change your diet, we're going to get you some exercise, we're going to limit your stress. These were patients with Alzheimer's disease. 70% of these people not only stabilized, but also, many of them improved in their cognitive function with Alzheimer's disease. Now, the beta-amyloid targeting drugs, they're never claimed to come anywhere, you know, to even stabilize the condition.

• 25:36Dr. Darshan Shah?

  Right.

• 25:36Speaker 01

  They mentioned that maybe they can slow it by a little bit. One half a point on an 18-point Alzheimer's scale is what they've been able to achieve at great cost and great risk. So, something, something ain't right here.

• 25:52Dr. Darshan Shah?

  Exactly.

• 25:53Speaker 01

  You know, I, I want to look, you know, I want to light the fire instead of, you know, curse the darkness here. But I think people have to be aware of what's going on. That's part of the mission.

• 26:04Dr. Darshan Shah?

  It makes zero sense. Like, I don't, to me, it's so surprising these drugs even got approved, that Medicare is covering them, that they're still out there. It's just massively confusing to me, right?

• 26:17Speaker 01

  As it relates to Lekembe, you know, the approval process is, it's mind-blowing. I mean, they had an expert panel of 12 people, researchers and clinicians that looked at, should we approve, should we recommend FDA approving this drug? This, and what they voted was, one abstained, one approved, and 10 said, no, we can't approve it. What did the FDA do? Approved it.

• 26:43Dr. Darshan Shah?

  Mind-blowing. Yeah, I mean, this is why we have conspiracy theories.

• 26:50Speaker 01

  I wish that were a conspiracy. I wish that were, then we could, you know, we could derogate the, the outcome. But it is a matter of fact. I mean, these drugs are FDA-approved, at least in America, and one wonders why.

• 27:03Dr. Darshan Shah?

  Yeah, it's crazy.

• 27:09Dr. Darshan Shah?

  So I'm 52 right now, but I'm still pushing all of my limits. I'm running long distances. I travel across many time zones to support my work. And I just want to live my life to the fullest. Staying active as I age isn't just about willpower. It's about supporting my mitochondria, the powerhouses of my cells, with the energy that they need to recharge my muscles and recharge my brain. Mitopure is a supplement that I take. It's backed by solid research showing that it can boost cellular energy, increase muscle strength, and support overall healthy aging. Personally, I take Mitopure every single day. It's helped me continue my active lifestyle, whether it's a high-intensity workout or keeping up with my kids.

• 27:51Dr. Darshan Shah?

  So if you are looking to support your body and want to feel younger from the inside out, my friends at Timeline are offering you a 10% discount on your first order. Go to timeline.com/drsah to get started. That's timeline.com/drsah. Your future self will thank you.

• 28:13Dr. Darshan Shah?

  So getting back to like the biology of this, you talked, you said a couple of times, your microglial cells. I know what those are. I've only talked about this a couple of times on my podcast in relationship to sleep, because we can see these microglial cells helping to clear toxins and byproducts of metabolism, basically, from the brain in nighttime when you're in deep sleep. But they go way beyond just clearance of byproducts of metabolism. So can you give us a little bit of a science education on what they are and how they work?

• 28:44Speaker 01

  Sure.

• 28:45Dr. Darshan Shah?

  And also can I add one more thing to that? I'm sorry.

• 28:47Speaker 01

  Okay.

• 28:47Dr. Darshan Shah?

  Can you also talk about how they are actually causing damage when they turn into their, like, evil step cousin, as you talked about?

• 28:55Speaker 01

  So again, let's, let's set this all up. The microglia, we hope, exist in what's called their M2 configuration. When they are in their M2 configuration, they are nurturing the neuron. They are creating an environment where new neurons can form. Who wouldn't want that? They're nurturing the synapse, where one neuron connects to the next synapse, and who wouldn't want that? They're actually keeping the blood-brain barrier intact. That's the good side. That's the brain defender side. They morph, under various circumstances that we've already alluded to, and we'll certainly unpack further, to becoming their M1 phenotype or configuration, where they are destroying neurons, destroying synapses, not allowing the growth of new synapses and neurons,

• 29:39Speaker 01

  and threatening the integrity of the blood-brain barrier. That's not a good thing.

• 29:45Speaker 01

  The reality is that they exist in a multitude of transitional forms. It's not as if they go from A to B overnight. They transition and can do good things and bad things. But we can actually measure in living humans M1 activated bad microglial cells. And it's called a TSPO scan. It's for research only. It's not available to people to have. And we see that this TSPO scan is lit up across every neurodegenerative condition that you could name to me right now. And in addition, in PTSD and in major depressive disorder and in long COVID. What is it telling you? That the, that these are neurological issues that are based upon the shift of the microglial cells.

• 30:29Speaker 01

  So we want to keep them in their supportive role. And many things can influence them to shift to being non-supportive. Primary among those we've talked about are our metabolic, our body's metabolic changes that causes these microglial cells to shift. Another thing that's really paramount, I think, in the discussion is that they respond to chemicals called inflammatory cytokines. And these are the chemical mediators of inflammation. When there's inflammation anywhere in the body, those chemicals can make their way to the brain and shift our microglial cells from supportive to being destructive. That can come from the gut.

• 31:10Speaker 01

  So we know that when we have increased gut permeability because of changes in our gut bacteria, our microbiome, that the permeability of the gut leads to inflammation in the body. And that now helps us understand why changes in diversity and function of the gut microbiome is associated with neurodegenerative conditions like Alzheimer's, like Parkinson's. You can almost fingerprint the microbiome now and determine Parkinson's, even Parkinson's risk. It's really quite breathtaking, but you know, for years, people have seen these relationships. But you know, the default was, well, you know, a disturbed microbiome leads to less production

• 31:53Speaker 01

  of important things for the brain, like short chain fatty acids and vitamins, and yes, the very neurotransmitters. But now through our understanding of this immunometabolism, the effects on the immune system, everything is really, not only getting very clear for us, but opening a lot of doors into, okay, we get it now, what can we do to fix it?

• 32:15Dr. Darshan Shah?

  Yeah, exactly. And so, you know, this triggering of these cells from going from M2 to M1, there are other things that do this. You know, we talked a lot about metabolic health. You mentioned also that there's gut dysbiosis that can do this. And you say in the book that a mechanism there is through this leaky gut and then LPS sneaking through the gut and then causing, LPS being bacterial fragments, causing inflammation as throughout the body. So that makes sense too, right? Obviously that's creating more inflammation, but there's a few things that are, might not be evident to some people that can also lead to activation of these destructive cells like proton pump inhibitors. Explain that one to me.

• 32:56Speaker 01

  Well, so the proton pump inhibitors play right into your conversation because they, you know, these drugs that people are taking, you know, that are so commonly available to people even over the counter, which is really kind of breathtaking. Because people think that, well, my gastrointestinal issues are related to having too much stomach acid. Yes, there are issues for which a proton pump inhibitor is indicated, and I list them in the book. But the idea that 20% of adults in America needs to block their stomach acid, which is the right, 50 million adults taking these drugs is really very, very worrisome. So we see them advertise on TV that people are eating a sausage sandwich and then think,

• 33:41Speaker 01

  oh, my stomach's upset, I'm going to block my stomach acid. That's not a good plan for 50 million Americans. Again, there is a medical indication for their use, but by and large, taking them over time leads to changes because you're changing the pH of the entire GI system. And that's going to favor the growth of some bacteria and suppress the growth of others. You're changing the normal array and functionality of the gut bacteria. And that has consequences. Well, what are the relationships? People who chronically take proton pump inhibiting drugs have about a 23% increased risk of dementia, a 32% increased risk of having a stroke.

• 34:22Speaker 01

  And interestingly, getting back to the discussion on the genes, the gene aspect carrying APOE 4, compared to APOE 4 people who aren't taking these acid blocking drugs, the risk for Alzheimer's in APOE 4 patients taking them is increased by about 68%.

• 34:42Dr. Darshan Shah?

  Oh my gosh.

• 34:43Speaker 01

  So right off the bat, and I put it in the book, if you carry APOE 4, you shouldn't be taking these proton pump inhibitors unless your doctor says you have one of the powerful indications for it, a gastric secreting tumor or Zollinger-Ellison syndrome, these things, we list them in the book, that people might need to take at least some form of acid blocking drug. But there are other forms. There are what we call the H2 antagonists that are not as associated with this risk. That said, you know, other drugs that are commonly used that increase this challenge to the gut are the NSAIDs, the non-steroid anti-inflammatory drugs like ibuprofen that

• 35:27Speaker 01

  ultimately change the gut milieu can increase permeability and lead to more inflammation. Wait a minute, did I just say that the anti-inflammatory drugs can lead to more inflammation? It's exactly what I said. So, you know, we need to really embrace the notion of above all do no harm, primum non nocere, that we've got to look at the potential downsides. And, you know, it goes without mentioning, but then I mention it. Why did I say it goes without mentioning? I don't know why people do that, right? Because eventually then we know I'm going to say it. That, you know, the biggest player are antibiotics.

• 36:08Speaker 01

  And that it's been, you know, published studies have indicated that about 50% of the prescribed antibiotics in America aren't really necessary. And why are we prescribing them? Because people, you know, you go into a walk-in clinic with a cough and you want to make sure you're walking out with a prescription for a Z-Pak or something. And if you didn't get it, you, I just wasted my money. But, you know, one important point that Dr. Martin Blaser brings out in his book, Missing Microbes, and, you know, people say, well, I never take antibiotics, is that 80% of the antibiotics manufactured in America are used in animals that we eat to make them

• 36:52Speaker 01

  fatter. So eating animals that have been treated with antibiotics poses a risk. We need to keep that in mind. That's why you see milk and poultry, et cetera, antibiotic free, because it's very real and very, very valid. So, you know, one study, I think was published in 2017, looked at, measured cognitive function in a group of women, comparing whether they had taken two months' worth of antibiotics in their whole midlife or not, and showed that those who had taken two months' worth additive, you know, it took a week here, a week there, or whatever, that there was

• 37:34Speaker 01

  significant increased cognitive decline in those who had experienced the antibiotic exposure. I want to make a very important point, and that is antibiotics are valuable. We all prescribe them. Of course we do. But we've got to, again, be judicious. And I talk about what people should be asking doctors, you know, instead of a broad spectrum antibiotics, should I use something that's more narrowly focused on the specific bacterium that you've identified is causing my UTI? Is it a gram negative? Then could we be real specific about the type of antibiotic that you're going to give me as opposed to weapons of mass microbial destruction?

• 38:14Dr. Darshan Shah?

  Right. And yeah, or even doing a culture first before prescribing the antibiotics and giving it some time to pick the right one.

• 38:22Speaker 01

  That said, technology is available now and, you know, looking at genomic studies to bypass culture altogether and get results within an hour.

• 38:34Dr. Darshan Shah?

  You're right.

• 38:35Speaker 01

  Why are we not using, why are we doing cultures anymore?

• 38:36Dr. Darshan Shah?

  Exactly. You're absolutely right about this.

• 38:38Speaker 01

  CNS, culture and sensitivity, that is so primitive, respectfully. You know, we really ought to be stepping up our game and identifying the organism, then prescribing a targeted antibiotic. In the future, I foresee that that antibiotic will be created as needed at the time of need in the emergency room when the organism is identified. A very specific and personalized approach for that infection, that organism, and let the rest of your microbiome remain unscathed.

• 39:11Dr. Darshan Shah?

  Yeah. You know, that's, I rarely go to the urgent care or never go to the emergency room, knock on one, thank goodness. But a few weeks ago, one of my kids was suffering like for a week with a cough. So we took him and they ran one of these genomic tests on his culture. It wasn't a culture, it was just on a specimen. And we found out within an hour, I was like, this is a miracle. Like, when did this happen?

• 39:34Speaker 01

  It happened many years ago.

• 39:36Dr. Darshan Shah?

  Wow. And we just now started using this.

• 39:38Speaker 01

  I know. And it's. Old habits die hard.

• 39:41Dr. Darshan Shah?

  Right, I guess so.

• 39:42Speaker 01

  People are down on what they're not up on, right?

• 39:44Dr. Darshan Shah?

  Exactly.

• 39:45Speaker 01

  So how cool was that?

• 39:46Dr. Darshan Shah?

  It's so cool.

• 39:47Speaker 01

  You knew in an hour.

• 39:48Dr. Darshan Shah?

  And we got the right antibiotic instead of, like you said, a weapons of mass destruction antibiotic. And it was effective within 24, 36 hours. It gave rid of his cough. Pretty incredible.

• 39:59Speaker 01

  Yes, the future looks bright. There is research ongoing right now that analyzes changes in signaling in the vagus nerve using AI that can identify sepsis before the white count goes up.

• 40:15Dr. Darshan Shah?

  Wow.

• 40:16Speaker 01

  That can identify sepsis and tell you the organism by measuring the transmission in the vagus nerve.

• 40:23Dr. Darshan Shah?

  No, come on, that's incredible. Yeah, the vagus nerve is a very smart nerve. And by listening to it with AI, we can certainly learn a lot. That's a

• 40:33Speaker 01

  Not only listening to it, but actually influencing it. I mean, you know, you know, the work being done by people like Dave Rabin, you know, ultimately valuing the vagus nerve by his peripheral stimulation of the parasympathetic nervous system and direct vagal nerve stimulation itself. I think the door is really being opened. And that plays a role in the microglial cells. So we really want to live our lives more in the rest and digest non-activated state as opposed to constantly being in sympathetic part of the nervous system, being overloaded, creating cortisol, threatening the gut integrity, threatening the hippocampal cells and threatening our microglial cells.

• 41:18Dr. Darshan Shah?

  Sure. You know, another trigger for the microglial cells that you mentioned in your book is glyphosate. And you mentioned a very specific mechanism there as well. Can we go into that a little bit?

• 41:28Speaker 01

  Well, there are multiple mechanisms, but this is a hot topic. I may be testifying very soon. There's in Washington, there's, you know, a lot of debate around glyphosate right now. There are groups that believe that it's necessary for our agriculture. And there are groups that believe that it represents a clear and present danger to human health. I respect both groups. I fall in the camp of the latter. And I think that when we look at the epidemiology studies that look at associations between Parkinson's risk and living near agricultural concerns that are using glyphosate.

• 42:07Dr. Darshan Shah?

  Like golf courses.

• 42:08Speaker 01

  Like golf courses and certainly even where various things are grown. That's important information. When we look at risk of a mother delivering a child that then develops autism spectrum disorder based on her proximity to agriculture that's using glyphosate, that's important information. But I think that the animal research that demonstrates significant microglial activation in the rodent model exposed to glyphosate and the fact that we know that glyphosate is a mitochondrial toxin doesn't bode well for it as it relates to what is going to happen to the brain. It is for these reasons.

• 42:49Speaker 01

  It sounds like the Shark Tank, it's for these reasons that I'm out. I wish you well, no. But for these reasons, I think we really have to take a second look. Again, above all, do no harm. You know, what's happening in America is a little bit more challenging that so much of the weeds have become glyphosate resistant or Roundup resistant such that glyphosate is no longer working. So now we are turning to an older herbicide that is far more threatening called Paraquat. 70 nations around the world have either reduced dramatically or all out banned the use of Paraquat. In the United States, the use of Paraquat is surging now, again, because glyphosate is becoming less effective.

• 43:34Speaker 01

  Paraquat is far more worrisome than glyphosate as it relates to being a direct and known mitochondrial toxin. In research laboratories, if you want to create Parkinson's in a primate, you expose it to Paraquat. That's how you make Parkinson's and we're putting it on our food. Something is seemingly very wrong with that equation. I would say that, you know, I want to have a respectful discussion about this. And here are both sides. There are those who would argue that we need to be using these herbicides to make sure that America remains the world's breadbasket or that we can at least feed our nation. I'm willing to listen to that.

• 44:17Speaker 01

  But I would be hopeful that those who believe that would be willing to listen to what I have to say about this as well.

• 44:23Dr. Darshan Shah?

  Yeah, wow. I'm glad you're fighting the fight on that because I think it's so important.

• 44:30Dr. Darshan Shah?

  Hi, Dr. Shaw here. I want to take a minute to talk to you about cellular health. So in my clinics, I've actually seen 30-year-old people with cells that look like they're pushing retirement. And I've also seen 60-year-olds with cells that look like they're 40 years old. So what's the difference? It's really about how fast their telomeres are breaking down. Your cells, you see, are like phones and they have limited cellphone battery. Poor sleep, stress, processed foods, all of these things can drain that battery way faster than it should. So this is the reason why I partnered with IM-8. IM-8 powers that cellular battery. It's not just another multivitamin. It's a comprehensive 92 ingredient formula designed specifically for cellular health and longevity.

• 45:15Dr. Darshan Shah?

  I'm talking 900 milligrams of vitamin C. That's like 20 oranges worth of DNA protection. The clinical dose of CoQ10 that you need to power your cellular engine. You also get zinc, selenium, vitamin E, alpha lipoic acid. All of these work synergistically for cellular repair and protecting your telomeres. So instead of taking a handful of pills every day and all these supplements, IM-8 actually gives you everything that you need in one scientifically formulated system. And this isn't just a theory anymore. IM-8 had partnered with Oxford University, the International Space Station, San Francisco Research Institute, and they've done studies and they've gotten this NSF certified to truly power your health.

• 45:58Dr. Darshan Shah?

  Most people are aging twice as fast as they should, unfortunately. You don't have to be one of them. Try IM-8. I actually have a discount secured for you. If you go to drshah.com/ima or go to im8health.com/discount/drsah and you can get 20% off with my discount code, drshah. You can also find the link below.

• 46:22Dr. Darshan Shah?

  And you know, you mentioned there's a pathway actually that humans don't have that is the whole kind of crux of the argument about why we're using glyphosate, right?

• 46:32Speaker 01

  Well, yeah, there is that argument made by the glyphosate manufacturer. Originally that was Monsanto, now Bayer, as you know, has bought that company. But it's that the cells that are targeted have something called the chicanate pathway for amino acid metabolism. And this isn't going to be on the quiz for your viewers, but anyway, the chicanate pathway is what is disrupted by glyphosate such that the plants that have not been genetically modified will die. Those that have been genetically modified, that's why they have these GMO seeds, are resistant to being hurt by glyphosate and they will thrive. So the weeds will die, the plant will thrive because it's genetically modified.

• 47:17Speaker 01

  Well, you know, the response is, well, yeah, human cells don't have the chicanate pathway. And that's true. Bacteria happen to have the chicanate pathway. So that becomes a problem in two regards. First, that the bacteria in the soil, the soil microbiome to have healthy plants is then destroyed. So you have to add more minerals and nutrients to the soil to grow a plant. The second thing is, guess what? Your body is seven, eight, nine, or 10 times more bacterial cells than Darshan Shah cells.

• 47:53Dr. Darshan Shah?

  Right, exactly.

• 47:54Speaker 01

  And so we are, many of those bacteria do in fact have the chicanate pathway. So it explains why there are clear and present dangers to the human microbiome posed by our exposure to glyphosate, which is detectable now in around 90% of American urine.

• 48:12Dr. Darshan Shah?

  Right. So that's my point for bringing that up is this, once again, this ties back to the gut-brain connection. You're disrupting the gut bacteria. You're creating gut dysbiosis, which then leads to more inflammation, activation of the microglial cells to the M1 state. And that's where the cascade kind of occurs.

• 48:32Speaker 01

  That's right. And the tools that we have right now that people need to embrace, that can allow A, this not to happen and B, if it already has, to help move them back to health as it relates to their brain are really straightforward. I mean, we get exotic, of course, people want that. I talk about current technology and future technology. The future looks great, but you know, most of the book is dedicated to the idea that, you know, one of the worst things you can do for your microglia is not get any exercise. Have a crappy diet. Get a bad night's sleep, you know, night after night. And we can fix those things right now.

• 49:16Speaker 01

  And it will have a huge payoff for your brain. If you don't get a good night's sleep, you dramatically increase your risk for metabolic issues like diabetes and Alzheimer's disease. Who knew? Well, I think I slept eight hours last night. Oh, did you? Well, yeah, well, how could you even ask that question? Well, because you're telling me you slept eight hours. Well, show me the data on your Apple Watch, on your Whoop, on your Our Ring, whatever device you're wearing or using. Because I need to know that you did in fact sleep for seven and a half to eight hours, eight and a half hours. And I need to know the quality of that sleep as well.

• 49:53Dr. Darshan Shah?

  Absolutely.

• 49:54Speaker 01

  Many, many people are surprised when they finally take a look at what's going on at night, that they awakened three times. They don't remember it, that they didn't really get enough deep sleep, where you activate what you talked about earlier, the brain's ability to clean itself out, that you are therefore threatening your microglial cells and paving the way for Alzheimer's. And I want to be super clear about one very important idea. And that is that the seeds are sown for this issue, Alzheimer's, and all neurodegenerative conditions earlier in our lives, in our 30s and 40s and 50s. Long before we forget the Wi-Fi code or grandchildren's names.

• 50:39Speaker 01

  That's well along the continuum. The metabolic issues that are occurring begin, they actually begin earlier than that, and we'll call it like it is. But I want my message today to really reach a lot of traction in that group of individuals who, you know, really fancy themselves as being really the avids as it relates to doing the right things. You need to know what's going on with your metabolism. You need to wear a CG, a continuous glucose monitor from time to time, know your fasting insulin level in addition to your fasting blood sugar, and know your A1C. And beyond that, know your homocysteine. We talk about various other laboratory studies that are very important, but

• 51:21Dr. Darshan Shah?

  Your acid levels.

• 51:22Speaker 01

  You, you bet, you're a cast, I've heard of that. Who knew? But know them when you're, you know, again, I've said it many times, the time to fix the roof is when the sun is shining. That's a quote from John F. Kennedy. And that's when we really want, and it's not just, I cut myself off, it's not just as it relates to risk for brain degeneration, it's for your brain function, you 30 and 40 and 50 year olds right now, to remain with a brain that is highly functional, allowing you to engage life, to be productive, to be more connective, to understand what your purpose is and really, you know, really go all in as it relates to doing the best you can because your brain is really highly functional.

• 52:05Dr. Darshan Shah?

  Yeah, I totally agree. And this is the whole mission of what we're doing here at Next Health. We're empowering people with the data, their biomarkers, their blood tests, their wearable devices. If only, still, I'm so surprised that only like 50% of people wear wearable, and then about half of those people don't even look at the data very often as well. So we've started looking at people's data for them to tell them like, this is how you really slept. This is what your glucose levels are really doing. So even if you're one of these people that has data anxiety and you don't want to look at it because it's overwhelming, I think it's

• 52:38Speaker 01

  That's always been a pushback. Yeah. But not generally from patients as much as physicians who want to poo poo the CGM.

• 52:45Dr. Darshan Shah?

  Yeah.

• 52:46Speaker 01

  Remember a few years back when CGMs were starting to get traction in the non-diabetic world? That there is an editorial published in JAMA saying that, oh, it's going to give people such anxiety and neuroses that there are with their data. And, you know, my response was, you know, if you're saying people shouldn't have data and should only be available by prescription under the guidance of a healthcare provider, then we shouldn't allow people to buy a bathroom scale.

• 53:14Dr. Darshan Shah?

  Right, exactly.

• 53:15Speaker 01

  Same thing, or to buy a blood pressure cuff at the pharmacy.

• 53:19Dr. Darshan Shah?

  But every individual should be able to make their own decision about their own body's data.

• 53:23Speaker 01

  And be empowered by their own data.

• 53:25Dr. Darshan Shah?

  Right, absolutely. And more often than not, once people understand the data and just takes a little bit of education, they get into it and they make changes and there's a feedback loop.

• 53:35Speaker 01

  It's, you're dedicating your energy and your knowledge base and your actions to, you know, again, be the arbiter of your brain and your body's destiny. And, you know, I know that's what you do at Next Health. And I was very honored when you asked me to be on the advisory board.

• 53:52Dr. Darshan Shah?

  Thank you.

• 53:53Speaker 01

  Because this is just exactly what needs to be happening right now with people. And you're making it happen. That's super cool.

• 54:00Dr. Darshan Shah?

  It is super cool, and we really need you on the advisory board because this message that Alzheimer's, neurodegenerative diseases in general can be prevented is a notion that sometimes, you know, people don't hear that from their traditional medical establishment physicians and practitioners. And it's one that they do need to hear because it's so empowering to hear that and then have the tools that you can actually use and the information to make that a reality for you as well.

• 54:29Speaker 01

  Well, you're kind of teeing up the next gen Next Health.

• 54:31Dr. Darshan Shah?

  And that's exactly.

• 54:32Speaker 01

  About something that may be in the offing, that we'll probably have to leave it at that. But more news at 11.

• 54:40Dr. Darshan Shah?

  Well, I do want to touch on it a little bit. Like, let's talk about some of the things that are coming. You know, we talked a little about GLP-1s, metformin also to help metabolic health. What's next?

• 54:51Speaker 01

  Well, there's a lot. I mean, if we're looking at what the future may hold or maybe what's available right now, there's some really cool things out there. There's work by Dr. Lee Wei-Sai at MIT, 40 Hz Light, you're familiar with it, but let's talk about it for your viewers.

• 55:06Speaker 01

  And what Dr. Lee Wei-Sai, actually, let me back up a little bit. Just talk about her TED Talk, which is how I got to know her, as we get to know a lot of people, then you reach out. She was talking about how she was, I think she was 12 years old. She was a little girl living in China. And she was walking in the market with her grandmother. And she said to her grandmother, it's time to go home. And her grandmother turned to her and said, home? What is home? Where is home? So she talks about that as being, you know, kind of the impetus for her desire to explore neuroscience. And researchers have determined that the, there's a beautiful orchestrated

• 55:50Speaker 01

  sound wave pattern in the brain called gamma oscillation. When we have good sinusoidal gamma oscillation in the brain, the microglial cells are happy, they're staying in their M2 configuration. The brain is, there's an orchestra playing a symphony and everything is beautiful. But when gamma is disrupted, it sets the stage for brain degeneration. The disruption of the gamma oscillation presages, comes before the accumulation of beta amyloid and the other shifts in the microglia that really are the, you know, the classic markers of Alzheimer's, if you will. So Dr. Lee Wei-Sai decided to explore what are the techniques we can use

• 56:32Speaker 01

  to help the brain reestablish this gamma oscillation, this beautiful background sinusoidal activity. And it was discovered that a specific flashing of light at specific frequencies would reestablish gamma oscillation in the rodent model, in the mouse model. They went through various frequencies of light and found that particularly at 40 flashes per second, gamma would be restored and importantly, microglia would be kept in their M2 configuration.

• 57:05Dr. Darshan Shah?

  Hmm.

• 57:06Speaker 01

  Amazing.

• 57:07Dr. Darshan Shah?

  Yeah.

• 57:08Speaker 01

  They did it in humans. They did it in patients that had Alzheimer's disease and demonstrated that there was increased functionality in various parts of their brains, that they evaluated them in terms of a scale that looked at their activities of daily living, dressing themselves, personal hygiene, et cetera, self-care, and found a dramatic reduction in their rate of decline in comparison to people who did not receive flashing of light at 40 times per second in their eyes with a mask and sound as well at 40 Hz. So that's incredibly exciting. What are the downsides? None. I mean, there are people who have what's called photoconvulsive epilepsy,

• 57:53Speaker 01

  meaning if they're exposed to flashing lights. So you screen for those. And what their company is doing is actually looking at how they measure brainwaves in people and tune that device just perfectly to get the most gamma frequency activity.

• 58:13Dr. Darshan Shah?

  So like on an individual basis, figuring out the rate of the flashing of the lights and the Hz of the sound waves.

• 58:20Speaker 01

  Right.

• 58:21Dr. Darshan Shah?

  To really improve the gamma activity of an individual person's brain.

• 58:25Speaker 01

  Having said that, 40 Hz generally is good. So you can buy that device. I have one on my desk at home.

• 58:31Dr. Darshan Shah?

  Really?

• 58:32Speaker 01

  I have a box that comes from a company called OptoSudix. I think they're here in California. And when I'm working, I have that light next to my monitor and you don't even know it's on, it's just light. Because they've created it in such a way that interspersed between the 40 Hz flash is another light that you don't, so therefore the light is very smooth.

• 58:53Dr. Darshan Shah?

  I see.

• 58:53Speaker 01

  And is it working in me? I don't know. I'm not that forgetful yet, so who knows? But I'm doing all the other things as well.

• 59:01Dr. Darshan Shah?

  Oh, that's amazing. This is available now.

• 59:03Speaker 01

  Oh, yeah.

• 59:03Dr. Darshan Shah?

  What was the name of the company again?

• 59:05Speaker 01

  That's called OptoSudix.

• 59:06Dr. Darshan Shah?

  OptoSudix, wow, okay. So see, this is something that most people might not even thought about, but the science is just progressing so rapidly and actually creating tools that are usable for people. Why not, why not try it?

• 59:20Speaker 01

  Yeah, and, you know, there's even about your home environment. So that's something you can do to change your home environment. You know, we pay attention to the quality of the water that we drink. Everybody, oh, I don't drink out of a plastic, I only go for the Mountain Valley or whatever the other brands are that come in glass. I do my very best, you know, sometimes in a hotel room, what are you going to do, of course? But you do the best you can when you travel. That said, yeah, our water is poor, what about the air we breathe? Shouldn't that be pure as well? And there's a lot being written about being, you know, the threats upon our brains by these PM 2.5, the particulate matter in the air from roads, from wildfire, from people burning incense.

• 1:00:05Speaker 01

  It's a clear and present danger, I use that term again, as it relates to the microglial cell. The relationship of PM 2.5 exposure in your environment to Alzheimer's risk is very real and very well described and is focused on what those PM 2.5s are doing to your microglial cells. Who knew? So we talk about it in the book. So I'm a huge, I've got a device at home in our bedroom that not only measures the quality of the air, but adjusts itself in terms of how strongly it's working based upon what it sees.

• 1:00:40Dr. Darshan Shah?

  Right.

• 1:00:41Speaker 01

  So, you know, day in and day out, I have a HEPA 14, that's the quality of the filter, on, on, on the job, day in and day out. So breathing good air.

• 1:00:51Dr. Darshan Shah?

  I tell everyone that, you know, I speak, whenever I'm speaking on stage, I'm like, the best thing you could do to protect yourself from environmental toxins is filter your air, right? And so where do you spend the most time? Probably your office, and probably your office at work and then your bedroom at night, and both those places would probably have a high quality.

• 1:01:09Speaker 01

  I look over and I see it and I feel so good.

• 1:01:11Dr. Darshan Shah?

  Yeah.

• 1:01:12Speaker 01

  Because it's always in the blue range.

• 1:01:13Dr. Darshan Shah?

  Right.

• 1:01:14Speaker 01

  It's always saying, your air is great. It measures a PM 2.5, right there are the air quality index.

• 1:01:20Dr. Darshan Shah?

  Yeah.

• 1:01:21Speaker 01

  And it tells you, you know, it tells you what's going on and that it's comforting. You get a good night's sleep knowing that your air quality is good.

• 1:01:28Dr. Darshan Shah?

  Yes, exactly. Lichen Air, that's the one that I use.

• 1:01:30Speaker 01

  Lichen Air. I've heard of that brand. L-I-C-H-E-N, Lichen Air. I'm on their board as well.

• 1:01:35Dr. Darshan Shah?

  You are amazing, guys. It's designed by a very famous doctor, actually, so it's a great, it's a great brand. You know, I have one more question for you. You have this mnemonic, Trem2. Can you talk about that one?

• 1:01:50Speaker 01

  Well, I didn't make up TRM2. It stands, it's an acronym.

• 1:01:55Dr. Darshan Shah?

  It's an acronym, sorry.

• 1:01:56Speaker 01

  Triggering receptor, triggering receptor expressed on myelocytes.

• 1:02:01Dr. Darshan Shah?

  Ah, okay.

• 1:02:02Speaker 01

  So TRM2 is the one of many receptors on the microglial cell. When it is stimulated, keeps the microglial cell on your side. TRM2 keeps it in M2, right? That's gonna be easy to remember. TRM2 for M2. So we want our TRM2 receptor to be plentiful and to be stimulated. Interestingly, our levels of TRM2, and there are genetic polymorphisms that are associated with reduced TRM2 production on our immune cells that are dramatically associated with increased Alzheimer's risk. So if you carry one of these genetic issues that are identified, then you have a dramatic

• 1:02:46Speaker 01

  increased risk of Alzheimer's, as one might expect. Because TRM2 means, less TRM2, so less M2, set the stage for Alzheimer's disease. But interestingly enough, beyond the genetic issue, if you are diabetic, you have less TRM2. If you are obese, you have less TRM2. And if you are both, which is pretty darn common here in America, then TRM2 levels are really, really reduced. So if you can work on your weight, and you can work on your diabetes, your TRM2 activation, your TRM2 sites are gonna be far more plentiful. And these TRM2 activities gonna be not just in your peripheral, you know, body as well, your myelocytes, but also on your microglial cells.

• 1:03:31Speaker 01

  So that explains to us why, another reason why obesity is associated with, in midlife, with increased Alzheimer's risk. You have less TRM2. Type 2 diabetes, we talked about it earlier, less TRM2. And interestingly, there is a pharmaceutical company involved in developing TRM2 agonists, or TRM2 targeting drugs. How cool is that? They get this, they say, well, if that's the way to keep our microglial cells in their M2 configuration, then, and that company was just bought by Sanofi for $420 million. And it's not a stock recommendation.

• 1:04:13Dr. Darshan Shah?

  Yeah.

• 1:04:14Speaker 01

  But that, a big, you know, major pharmaceutical company now is embracing, you know, there's more to the story than beta amyloid. There's more that we can do.

• 1:04:24Dr. Darshan Shah?

  Yeah.

• 1:04:25Speaker 01

  The other, you know, interesting thing is, again, targeting this mitochondrial function. Because mitochondria dictate M2 versus M1. Metabolism, immunometabolism. And as we see these ways of targeting mitochondrial function from a pharmaceutical perspective, you mentioned metformin, that's something we should be looking at, rapamycin. But knowing that we can augment our mitochondrial function by involving ourselves in something called exercise, who knew? Getting a good night's sleep, some supplements like coenzyme Q10, urolithin A, taking essential fatty acids, and very important for mitochondrial function. You know, all of these things conspire and build a program.

• 1:05:10Speaker 01

  You know, people talk about layering these things one on top of each other, or what's it called, the stack? You know, what's in your stack? That's certainly a dzier, a kind of a terminology, but it's, is it life and death? Absolutely. This is a life and death decision. You bet.

• 1:05:27Dr. Darshan Shah?

  And I think also, you know, the side benefit of avoiding Alzheimer's is, you feel great. Like, if you're metabolically healthy, you have good functioning mitochondria, you're sharp, you wake up with energy every day, chances are, you're not obese, and you are able to keep fat off.

• 1:05:43Speaker 01

  Those are the side effects.

• 1:05:44Dr. Darshan Shah?

  These are the side effects, right?

• 1:05:45Speaker 01

  Yeah, these are the side effects of doing what we're describing here. And again, you just said the term avoiding Alzheimer's. Think about that. I mean, you know, a few years back, Alzheimer's prevention would be almost heretical.

• 1:05:58Dr. Darshan Shah?

  Heretical, right.

• 1:05:59Speaker 01

  And now there's a Journal of Prevention of Alzheimer's. The Journal of Prevention of Alzheimer's, which is interestingly where that ultra-processed food study that I quoted earlier was published. So a whole journal dedicated to the idea that we can prevent this potentially pandemic event, that is, it's breathtaking. We've reached a new level of nurture, of love, you know, of really giving people this information and letting them be the architects of their brain's future. So it's, it's a very wonderful time.

• 1:06:34Dr. Darshan Shah?

  Yeah, it really is. And I can't wait to dive into your book even further. And like I said, I feel like it's a culmination of everything you've written, and probably there's a little piece of every one of your other books inside of this book, so I'm just really looking forward to it.

• 1:06:49Speaker 01

  It really brought together everything I've been doing. I mean, you know, you know what I've been interested over the years? And we, we talked about highly processed foods in Grain Brain before there was even the term ultra-processed foods. Now that, you know, I'm avoiding ultra-processed foods, I'm making fun of that. That's exactly what you wanna do. And the microbiome, and uric acid, and, you know, all the things. They've all converged through the notion of immunometabolism on these microglial cells and your brain's destiny. So you're right, it's a time of, I think, connecting a lot of dots, a lot of hanging chads.

• 1:07:26Dr. Darshan Shah?

  Yeah. Well, thank you for being on the podcast.

• 1:07:30Speaker 01

  You bet.

• 1:07:31Dr. Darshan Shah?

  Educating me and my audience for something, for a topic that's incredibly important. Really appreciate having you.

• 1:07:37Speaker 01

  Thank you. Delighted to be here, always.

• 1:07:39Dr. Darshan Shah?

  And Dr. Perlmutter, if someone's been hiding under a rock and doesn't know where to learn from you, where can they go?

• 1:07:44Speaker 01

  Well, Dr. Shah, the page for the book, which is called Brain Defenders, is strangely, braindefenders.com. Who knew? And there, there's a link to all the major online retailers and a bunch of bonuses that people get when they preorder the book. My new website, which we launch next week, I'm very excited to say, is drperlmutter.com, undergoing a dramatic facelift, drperlmutter.com.

• 1:08:11Dr. Darshan Shah?

  Okay.

• 1:08:12Speaker 01

  And there you go.

• 1:08:13Dr. Darshan Shah?

  Thank you so much, once again, and look forward to having you back again.

• 1:08:17Speaker 01

  I'm looking forward to it.

• 1:08:18Dr. Darshan Shah?

  Thank you. Thank you so much for listening to the podcast today. Please remember to subscribe if you liked this episode, and give us a good review, and share a link with your friends. It really helps to support all of our efforts. I also want to remind you that the information shared on this podcast is for educational purposes only, and is not intended to replace professional medical advice, diagnosis, or treatment. Please consult with your healthcare provider or physician before making any decisions or taking any action based on what you hear today, especially if you have any underlying health conditions or on any medications. Your doctor knows your personal health situation the best, and it's always important to seek their guidance.