306. The Alzheimer's Drug With a 25% Brain Bleed Risk - Dr. David Perlmutter

You might think Alzheimer's starts in your 70s. Dr. David Perlmutter explains why it begins decades earlier, and how the p-tau 217 blood test flags risk long before symptoms appear. Gary Brecka and Dr. Perlmutter break down microglia, insulin resistance, pre-diabetes, APOE4, homocysteine, vitamin D, creatine and sleep, plus what the POINTER study showed about cognitive decline in metabolically compromised adults. CLICK HERE TO BECOME GARY’S VIP!: https://bit.ly/4ai0Xwg Get Dr. David Perlmutter’s book, “Brain Defenders”: https://bit.ly/4xvoYtY Listen to Dr. David Perlmutter on all your favorite platforms! YouTube: https://bit.ly/46rZjan Spotify: https://bit.ly/4dxPdZl Apple Podcasts: https://bit.ly/4dBz19u Connect with Dr. David Perlmutter Website: https://bit.ly/4yEhBBk YouTube: https://bit.ly/46rZjan Instagram: https://bit.ly/3VgElZH Facebook: https://bit.ly/4xvTC6v TikTok: https://bit.ly/4xXDcEM X: https://bit.ly/4xxJdal LinkedIn: https://bit.ly/4yfpNIF Thank you to our partners A-GAME: “ULTIMATE15” FOR 15% OFF: http://bit.ly/4kek1ij AION: “ULTIMATE10” FOR 10% OFF: https://bit.ly/4h6KHAD AIRES: “ULTIMATE20” FOR 20% OFF: https://bit.ly/4a3Duze BAJA GOLD: “ULTIMATE10” FOR 10% OFF: https://bit.ly/3WSBqUa BODYHEALTH: “ULTIMATE20” FOR 20% OFF: http://bit.ly/4e5IjsV COLD LIFE: THE ULTIMATE HUMAN PLUNGE: https://bit.ly/4eULUKp CYMBIOTIKA: “BRECKACYM30” FOR 30% OFF: https://bit.ly/4tjyluP GENETIC METHYLATION TEST (UK ONLY): https://bit.ly/48QJJrk GENETIC TEST (USA ONLY): https://bit.ly/3Yg1Uk9 GOPUFF: GET YOUR FAVORITE SNACK!: https://bit.ly/4obIFDC H2TABS: “ULTIMATE10” FOR 10% OFF: https://bit.ly/4hMNdgg HEALF: 10% OFF YOUR ORDER: https://bit.ly/41HJg6S PEPTUAL: “TUH10” FOR 10% OFF: https://bit.ly/4mKxgcn SNOOZE: LET’S GET TO SLEEP!: https://bit.ly/4pt1T6V WHOOP: JOIN & GET 1 FREE MONTH!: https://bit.ly/3VQ0nzW Watch the “Ultimate Human Podcast” every Tuesday & Thursday at 9AM EST: YouTube: https://bit.ly/3RPQYX8 Podcasts: https://bit.ly/3RQftU0 Connect with Gary Brecka Instagram: https://bit.ly/3RPpnFs TikTok: https://bit.ly/4coJ8fo X: https://bit.ly/3Opc8tf Facebook: https://bit.ly/464VA1H LinkedIn: https://bit.ly/4hH7Ri2 Website: https://bit.ly/4eLDbdU Merch: https://bit.ly/4aBpOM1 Newsletter: https://bit.ly/47ejrws Ask Gary: https://bit.ly/3PEAJuG Timestamps 00:00 - Intro of the Show 01:33 - Grain Brain and ultra-processed carbohydrates 03:26 - Pre-diabetes decades before any symptoms 08:03 - Type 3 diabetes and insulin in the brain 11:48 - The fasting insulin level to target 14:08 - Immunometabolism and your microglial cells 16:12 - APOE4 as predisposition, not destiny 19:25 - Inflammation from the gut, mouth and air 25:50 - Aerobic vs resistance training for the brain 30:04 - Sarcopenia, myokines and BDNF 34:44 - Mitochondria and the TSPO brain scan 40:11 - The Tanzi, Ornish and POINTER trials 46:31 - Beta-amyloid drugs and the Cochrane data 55:00 - Sleep, the glymphatic system and insulin 58:25 - Creatine dosing and the creatinine confusion 1:03:52 - Vitamin D, VDR polymorphisms and tau 1:09:35 - Fish oil, DHA and the omega-3 study 1:12:48 - Homocysteine, B complex and MTHFR 1:18:43 - Red light, RNS60 and mitochondrial transplant 1:27:11 - Isolation, cortisol and oxytocin 1:32:58 - What it means to be an ultimate human Disclaimer: This podcast is for informational purposes only and does not provide medical advice. It is not intended for diagnosing or treating any health condition. Always consult a licensed healthcare professional before making health or wellness decisions. Gary Brecka is the owner of Ultimate Human, LLC which operates The Ultimate Human podcast and promotes certain third-party products used by Gary Brecka in his personal health and wellness protocols and daily life and for which Ultimate Human LLC and / or Gary Brecka directly or indirectly holds an economic interest or receives compensation. Accordingly, statements made by Gary Brecka and others (including on The Ultimate Human podcast) may be considered promotional in nature. Learn more about your ad choices. Visit megaphone.fm/adchoices

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

• 0:00Speaker 00

  Alzheimer's is an almost uniformly fatal condition, the third leading cause of death in adults in America.

• 0:05Gary Brecka?

  You know, there's a lot of theories around Alzheimer's and accelerated brain aging, but many of them point to insulin resistance and high blood sugar as one of the hallmarks of accelerated neurocognitive decline.

• 0:17Speaker 00

  90% of America's prediabetic patients don't know it because you get your annual blood work, you get a pat on the back, well, you're not diabetic yet, go home and hope for the best. I really reject that in the face of 7.6 million Americans now diagnosed with Alzheimer's with being prediabetic being a huge entree to that event.

• 0:37Gary Brecka?

  I think there are a lot of people that my age that are dealing with aging parents, and I'm hell bent on turning this around for my mother and to the extent that I can prevent it for other folks like my kids, that's a service that I think is well met. I'm hell bent on getting this message out that you could rewrite your destiny as it relates to your brain, and you absolutely can do it, and you just need the tools. In these conditions like Alzheimer's, patients are not losing their memory per se, they're losing access to their memory. What do we do now to try to restore that access? You know, ultimately, I think well beyond what I describe here is

• 1:22Gary Brecka?

  Hey, guys, welcome back to the Ultimate Human Podcast. I'm your host, human biologist Gary Brecka, where we go down the road of everything anti-aging, biohacking, longevity, and everything in between. And today's podcast guest is a very, very, very special guest to me. He doesn't even realize this, but in the 300-plus episodes that we've done on the ultimate human, only one other time have I used this next phrase, that I am sitting down with someone that I consider one of my early mentors in this space. The first time I used that was with Mark Hyman, because I had read most of his New York Times bestselling books.

• 2:01Gary Brecka?

  And in 2014, I read a book that this gentleman authored called Grain Brain, and it entirely and permanently changed the trajectory of my career. So, Dr. David Perlmutter, welcome to the podcast.

• 2:14Speaker 00

  Well, I'm delighted to be here today. It's very special to be here, too. I love this area of the world, very, has a lot of meaning for me.

• 2:20Gary Brecka?

  Yeah, you know, I learned something very special before the podcast today. I walked into my kitchen and he was FaceTiming with my father-in-law, and it turns out that my wife's father built your doc 40 years ago.

• 2:33Speaker 00

  That's right.

• 2:34Gary Brecka?

  That's a wild connection that we have, but the working

• 2:38Speaker 00

  Yeah, it's true. It's a small world, though. I mean, who knew?

• 2:41Gary Brecka?

  It's a small world. But I read Grain Brain, I want to say you wrote it in 2013, but I read it in 2014.

• 2:49Speaker 00

  So, yeah, it was published in 2013, wrote it in 2012, obviously. And, you know, that book focused, I think, on something that's now pretty well-understood and embraced, that eating a diet that features a lot of highly-processed carbohydrates is a bad thing for the brain. That was my contention back then, and, you know, it was a great success, the book was a great success, but I got a lot of heat from my colleagues. That, I mean, what do carbs have to do with the brain? How could you make such a statement? We didn't have the term back then of ultra-processed foods. Now, of course, that's what we're talking about, and then ultra-processed carbohydrates being under that umbrella. And now we see really great data coming out, that higher consumption of these foods that

• 3:34Speaker 00

  are modified such that they're going to raise your blood sugar, threaten the functionality of your insulin, and at the same time are devoid of things that you need, like dietary fiber to nurture your microbiome, that these happen to be really threatening for your metabolism. And guess what? The brain is intimately involved with metabolism, either being supportive or being destructive.

• 3:57Gary Brecka?

  And, you know, I'm going through this right now, I've been very public about this on my platform with my own mother. And, you know, I'm upset with myself in a lot of ways, because as I really peel back the layers of the onion, she was hyperglycemic or highglycemic, you know, insulin-resistant and prediabetic for almost 20 years, that we can go back and find. And, you know, there's a lot of theories around Alzheimer's and accelerated brain aging, but many of them point to insulin resistance and, you know, high blood sugar as one of the hallmarks of accelerated neurocognitive decline.

• 4:42Speaker 00

  I want to stop you right there, and I want your audience to remember what you just said, because you said something I think that is fundamental. You said, "for 20 years." Long before her cognitive impairment was noticeable.

• 4:56Gary Brecka?

  Yeah, but she didn't have diabetes, which is why they didn't treat it.

• 4:59Speaker 00

  Doesn't matter.

• 5:00Gary Brecka?

  Yeah.

• 5:01Speaker 00

  That's why we're here today. That's the discussion I think that we are going to have today, and that is that when you begin to have these cognitive issues, forgetting why you walked into the room, the Wi-Fi code, the grandchildren's names, whatever it may be, that situation has been brewing for decades. So that's what our target then needs to be. It's the people in their 30s and 40s who are watching us right now, thinking, well, they've got time, because, well, Alzheimer's begins in your 70s. It does not. That's when the clinical manifestations begin, and that's when modern mainstream Western medicine begins to think, oh, there's something we need to do.

• 5:38Gary Brecka?

  Right.

• 5:39Speaker 00

  I'm going to tell you a quote from an 81-year-old man, who was the oldest person to sign the Constitution of the United States of America, and actually sign not only the Constitution, but the Declaration of Independence, Benjamin Franklin.

• 5:54Gary Brecka?

  Wow.

• 5:55Speaker 00

  One of his famous quotes is, "An ounce of prevention is worth a pound of cure."

• 5:59Gary Brecka?

  Oh, yeah.

• 6:00Speaker 00

  We are focused in America, to be fair, on the pound of cure. We're focused on the development of drugs to take care of people, to cure their illnesses, when just giving them the tools to prevent them 20, 30, 40 years prior to their onset or to the manifestation is really, makes sense from an economic perspective, it makes sense from a health and longevity perspective, and it absolutely makes sense from an emotional perspective, too, knowing fully what you are experiencing right now, because I've been there.

• 6:33Gary Brecka?

  Yeah. And we're now trying to backtrack and catch up for the last two-plus decades, and it may have been even longer, we just have data from 20 years ago, and knew that she was prediabetic, but never really tripped into the full diabetes range, so never really got care for it. I mean, maybe in some ways, had she done that, there would have been a lot more Well, you're talking about a third of American adults are prediabetic, and here's the gripping

• 7:03Speaker 00

  part of that statement, and it fits perfectly with what you're describing. 90% of America's prediabetic patients don't know it.

• 7:10Gary Brecka?

  Right.

• 7:11Speaker 00

  Because you get your annual blood work, you get a pat on the back, well, you're not diabetic yet, go home and hope for the best.

• 7:19Gary Brecka?

  Right.

• 7:20Speaker 00

  And do whatever it is you're doing. I really reject that. I really reject that in the face of 7.6 million Americans now diagnosed with Alzheimer's with being prediabetic being a huge entree to that event.

• 7:34Gary Brecka?

  Yeah.

• 7:35Speaker 00

  We've got to pay attention. We owe it to people to call this out, and to really just sort of challenge this notion that annual blood work is enough, and the idea of being in the normal range is something we should be thinking is a good thing.

• 7:50Gary Brecka?

  Yeah, or just not having disease.

• 7:52Speaker 00

  Right. I want everyone I relate to to be in the optimal range. I want to optimize health, and therefore, ounce of prevention worth a pound of cure. Keep these people healthy, and recognize that, again, the seeds are sown metabolically for developing Alzheimer's in your 30s and 40s and 50s. It doesn't just happen. There's something called a heart attack. You are perfectly fine, you're walking down the street one day, and all of a sudden this thing out of the blue comes and attacks you, narrows, shuts down your LED, and down you go. That's not how it worked. It didn't just attack you out of the blue. You've been dealing with that for an awful long time, that narrowed your coronaries. So, you know, this is the mission, and I think

• 8:37Speaker 00

  Our time together today is to really raise up the sense of empowerment. That here's the knowledge and here's what you need to do. Here's how you can keep your brain healthy. If you live to be age 85, and I'm sure that's your plan.

• 8:53Gary Brecka?

  Yeah.

• 8:53Speaker 00

  And I'm sure that's the plan of everybody watching this right now.

• 8:56Gary Brecka?

  My parents were 82 and 81.

• 8:56Speaker 00

  Right. Your risk is 40 to 50%. That's basically a flip of a coin of becoming an Alzheimer's diagnosed individual or not. And the purpose of our time together right now is that you can influence that risk dramatically. In the time, as John Kennedy said, the time to fix the roof is when the sun is shining.

• 9:20Gary Brecka?

  Right. Wow. You know, do you subscribe to the fact, I mean, some, some folks will say that Alzheimer's is type 3 diabetes, insulin resistance in the brain. And I don't think Alzheimer's is one thing. There are genetic predispositions. There are lots of, I guess, multifactorial.

• 9:37Speaker 00

  We've got a lot to talk about today. She was, you know, that's a term. And it's a term, I think that's a bit myopic. And because it's more than just insulin resistance in the brain. That plays an important role. But insulin isn't really having a huge effect on a lot of the brain. There are four major areas, the hypothalamus, the hippocampus, prefrontal cortex, and the olfactory bulb. Why is that important? It is important because those areas are involved in Alzheimer's, the olfactory bulb. Why do Alzheimer's patients often lose sense of smell early on, even before their cognitive dysfunction becomes manifest? The hippocampus, their memory center, of course, central player as it relates to Alzheimer's.

• 10:22Speaker 00

  The hypothalamus, yes, Alzheimer's patients become metabolically dysfunctional. Being metabolically challenged with insulin resistance sets the stage for it. But at the same time, the brain becomes, dysregulates metabolism from the hypothalamus, worsening the problem. And finally, the prefrontal cortex, I'm pointing to my forehead because that's where it lives, allowing us to carry out purposeful executive, what we call executive function. Planned activities, planning for the future, thinking about outcome, relating to other people, recognizing what I do to myself today might affect me tomorrow. Those are fairly sophisticated human attributes that begin to decay as Alzheimer's manifests.

• 11:06Speaker 00

  So those areas of the brain basically require insulin for their functionality. Other areas of the brain, not so much. But beyond that, insulin is more important than just helping regulate blood sugar and drive blood sugar into a cell for metabolism. Insulin in the brain is what we call a trophic hormone. You and I had a talk over lunch about BDNF, brain derived neurotrophic factor, a trophic hormone. And in a very real way, insulin acts in the same way, nurturing neurons, nurturing synapses. And, you know, in that regard, we need functional insulin in the brain.

• 11:45Speaker 00

  So the idea is then, if this insulin lack of function gains the moniker, type 3 diabetes for these reasons, I can live with it. But that has prompted research into the administration of intranasal insulin to help correct the problem or override the problem. And I have mixed feelings about that. It's the reason, that one reason I sort of reject it is because, why do we now give insulin for type 2 diabetics? I don't fully understand it. They already have very high insulin levels. But the insulin isn't working because their blood sugars have been elevated for so long.

• 12:28Speaker 00

  So they're, one of the earliest markers that we want to look at is fasting insulin level. Because that predicts that your blood sugar is going to raise or rise, I guess would be more appropriate. But, you know, the idea of giving insulin, well, it'll bring the blood sugar down, no question. But we've got to do better than that. I mean, we've now seen over the past decade, how dramatically effective in a type 2 diabetic, a ketogenic diet can be.

• 12:54Gary Brecka?

  Yes.

• 12:54Speaker 00

  To reestablish insulin functionality, not insulin quantity, but the function of the insulin that we already have.

• 13:01Gary Brecka?

  The sensitivity of the insulin itself.

• 13:03Speaker 00

  The function of that insulin. And to, go ahead.

• 13:05Gary Brecka?

  Well, I was gonna say, what is a good fasting insulin level? I mean, because when people get a blood panel and they've got fasting glucose, hemoglobin A1C, three month average of the blood sugar, and then insulin.

• 13:16Speaker 00

  Between three and five.

• 13:17Gary Brecka?

  Between three and five.

• 13:17Speaker 00

  And that is really low.

• 13:18Gary Brecka?

  Yeah, it is.

• 13:19Speaker 00

  It is. And you and I are talking optimization here today.

• 13:23Gary Brecka?

  Yeah.

• 13:24Speaker 00

  We're talking pre-Alzheimer's.

• 13:26Gary Brecka?

  Right.

• 13:26Speaker 00

  You know, we, what the heck is that term? Pre, well, we know prediabetic because the blood sugar is starting to rise. Well, we have a pre-Alzheimer's when you are metabolically compromised. How do you know? You know, because your blood sugar is elevated, your fasting insulin is coming up, your A1C is elevated, your waist to hip ratio is increasing, your belly is getting bigger, your blood pressure is going up. These are metabolic issues that are changing the function of your brain's immune cells and creating a brain environment that is threatening to your synapses. Maybe I want to unpack that a little bit more.

• 14:03Gary Brecka?

  Yeah, no, I definitely, this is the route that I want to go. Cause I have a very selfish reason for.

• 14:08Speaker 00

  That's all right.

• 14:09Gary Brecka?

  Having you on the podcast today. But, but also I think there are a lot of people that my age that are dealing with this, with, with aging parents. And I'm hell bent on turning this around for my mother and to the extent that I can prevent it for other folks. You know, like my kids and, and their kids, you know, that's, that, that's a service that I think is, is well met.

• 14:30Speaker 00

  And it's, it's certainly for you. But can you imagine putting your kids through your cognitive decline? What that would be like for them?

• 14:39Gary Brecka?

  Yeah.

• 14:39Speaker 00

  You're getting, you're, you're getting a sense of that right now, what you're going through. And you don't want your kids to go through that.

• 14:44Gary Brecka?

  That's exactly it.

• 14:45Speaker 00

  You know, I watched my brilliant brain surgeon father die of this disease.

• 14:50Gary Brecka?

  Really?

• 14:50Speaker 00

  While I am a practicing neurologist and I had nothing to offer him.

• 14:55Gary Brecka?

  Wow.

• 14:55Speaker 00

  And it's, it's challenging. It really is challenging. What do you do with that?

• 15:02Gary Brecka?

  Right.

• 15:02Speaker 00

  And then you just use the term hell bent. So I'm hell bent on getting this message out that you could rewrite your destiny as it relates to your brain. And you absolutely can do it and you just need the tools. And your audience already knows what these tools are to some degree. We'll talk about some leading edge kind of stuff in a minute. But your very first podcast dealt with metabolism.

• 15:25Gary Brecka?

  Yes.

• 15:25Speaker 00

  Think about that.

• 15:26Gary Brecka?

  Yeah.

• 15:26Speaker 00

  And we now have a term called immunometabolism, the relationship of the immune system to metabolism. Holy Toledo, how does that work?

• 15:36Gary Brecka?

  Yeah.

• 15:36Speaker 00

  We know intimately that your brain's immune system is responsive to your body's metabolism. Your brain's immune system made up of what we talk about in this book, the microglial cells, allows those microglial cells to nurture your synapses, to love your neurons, to shore up the blood brain barrier, or those microglial cells, when your metabolism is threatening, will shift to becoming the evil twin.

• 16:04Gary Brecka?

  Wow.

• 16:05Speaker 00

  And when those microglial cells become the evil twin, they destroy synapses. They cause lack of connection in the brain, loss of connectivity. They threaten the neurons and they destabilize the blood brain barrier. That shift of those immune cells from being what we call M2 supportive, brain defenders, to being destructive is dictated by their metabolism. And their metabolism mirrors your body's metabolism.

• 16:33Gary Brecka?

  Wow.

• 16:34Speaker 00

  Home run.

• 16:35Gary Brecka?

  Wow. So you know, like, the, the notion that all cancer, regardless of its form or origin, was at one time a healthy cell. And what happened to that cell? It shifted its metabolism. And that shift in metabolism now produces a cell that takes as many lives only, is second only to cardiovascular disease.

• 16:59Speaker 00

  And third on the list? Alzheimer's.

• 17:02Gary Brecka?

  Yeah, Alzheimer's.

• 17:03Speaker 00

  Think about that.

• 17:04Gary Brecka?

  Wow.

• 17:05Speaker 00

  Who? Alzheimer's is an almost uniformly fatal condition.

• 17:10Gary Brecka?

  Yeah.

• 17:11Speaker 00

  The third leading cause of death in adults in America.

• 17:14Gary Brecka?

  Wow.

• 17:15Speaker 00

  So let's contextualize this a bit, that we're spending, you know, 360 billion with a B on caring for Alzheimer's patients for a disease that I will tell you today is largely preventable.

• 17:30Gary Brecka?

  Now, there is a genetic predisposition. So are you talking about in the non-predisposed?

• 17:35Speaker 00

  Nope. I am talking about those individuals more specifically than you can imagine.

• 17:40Gary Brecka?

  Wow.

• 17:40Speaker 00

  So we do know that if you carry one or two APOE4 alleles, as many of your audience, I'm sure, understands, because they've had their blood work done, that you have a, as you characterize it, predisposition. Great word, not destiny.

• 17:55Gary Brecka?

  Right.

• 17:55Speaker 00

  Predisposition is not destiny.

• 17:56Gary Brecka?

  Right.

• 17:57Speaker 00

  So we, we see the studies now that indicate that dramatic lifestyle changes can absolutely offset that genetic predisposition. I mean, these people get back their genetic stuff with the printout that says, basically, put your wagons in a circle because you're in deep trouble.

• 18:12Gary Brecka?

  Right.

• 18:13Speaker 00

  And I'm here to say to, you know, all of your audience, that is just not true. And I'm talking to 25% of your audience right now. Got their genetics back, saw the APOE4 and said, I'm basically screwed. It's just miss, it's just misinformation. So there's so much that can be done.

• 18:32Gary Brecka?

  People ask me health questions every single day about their labs, their sleep, their supplements, their genetics. I want to help every single one of them. And that's why I built Just Ask Gary. It's an AI trained on everything I know, including my protocols, my research and my methodology. You ask the question, you get my answer, any time of the day. Go to theultimatehuman.com/AI and check it out. Now let's get back to the Ultimate Human Podcast. So I want to get very specific with you and, and really get deep into the book. But what does that lifestyle look like? 30s, 40s, I'm in my 50s. I believe that I'm living it now, but the previous two centuries, not so much.

• 19:15Speaker 00

  So I've got to over correct? Yeah. No, I know that feeling very well. We were talking, yeah, I mean, even the head trauma part. Yeah. And I, I remember lying on the mat, being counted out by the ref, one. Cause I couldn't get up after I got kicked in the head in a, in a match of some sort back in the day.

• 19:33Gary Brecka?

  Karate tournament?

• 19:33Speaker 00

  Yeah, it was, it was, before they had MMA, they had, it was full contact karate. And I, you know. Nothing can harm me, right?

• 19:42Gary Brecka?

  Sounds like a great idea.

• 19:43Speaker 00

  It was a great plan, you know, and no headgear.

• 19:45Gary Brecka?

  It was a great plan.

• 19:46Speaker 00

  No headgear at all.

• 19:47Gary Brecka?

  Yeah.

• 19:48Speaker 00

  And, and, you know, there were several other events that I, you know, had a, but anyway, and, and my lifestyle choices back in the day when you were hard, uh, you were just like impervious to these events, they accumulate over time, they manifest in the changes in your metabolism, you can watch it happen if you're looking. So that's a point I want to make, you really want to be matricizing, you want to wear your, uh, Oura ring, or Apple watch, or whoop, whatever it may be, and find out that, what is the duration and quality of your sleep? Very important. What is your blood sugar doing? Wear a CGM, continuous glucose monitor from time to time. Get your blood work done, you know, you can do that without a doctor now and get that information, then you challenge yourself with the question, well, what do I do with

• 20:33Speaker 00

  this information? You know, we'll, we'll talk about what that, and I put parameters in the book about what things should look like, but, you know, ultimately, I think, uh, well beyond the, the, what I described here is availing yourself of a more personalized medicine approach in a clinical situation that's using AI to determine what's best for Gary Brecka that would be different than David Perlmutter.

• 20:57Gary Brecka?

  Right.

• 20:58Speaker 00

  You want to know that.

• 20:59Gary Brecka?

  Right, very specific, personalized medicine.

• 21:01Speaker 00

  And that's, that's state of the art right now.

• 21:04Gary Brecka?

  And it's, and it's widely available, by the way.

• 21:06Speaker 00

  Absolutely, widely available. So, let me, I didn't answer your question.

• 21:09Gary Brecka?

  Yeah.

• 21:09Speaker 00

  I want to apologize. So the question was, then, what are the things that shift these microglial cells? And we mentioned metabolism, so all the metabolic issues will shift microglial cells away from being supportive to being destructive. That is the, the fundamental now across the entire spectrum of neurodegenerative conditions. Alzheimer's, Parkinson's, MS, multi-system atrophy, uh, progressive supranuclear palsy, um, uh, long COVID, uh, post-traumatic stress disorder, major depressive disorder. Who knew? These are not considered neurodegenerative conditions, but they shift the microglia and set the stage for brain degeneration. We've got to pay attention to that.

• 21:53Speaker 00

  So this understanding of immunometabolism, the relationship with the brain's immune system, in fact, your entire body's immune system to the, the state of health of your metabolism is profound, it's a bit iconoclastic, and it is certainly empowering.

• 22:12Gary Brecka?

  Hmm. Yeah, I noticed you don't call it autoimmune, like autoimmune microglial, so.

• 22:19Speaker 00

  Well, and I, I was just asked that question because, um, it's not a classic rheumatoid arthritis, systemic lupus erythematosis, ankylosing spondylitis type of Crohn's disease.

• 22:31Gary Brecka?

  It's not an antibody to.

• 22:33Speaker 00

  Yeah.

• 22:34Gary Brecka?

  A neuron.

• 22:35Speaker 00

  It is not antibody directed, it's not a molecular mimicry where there's, uh, on the, a cell surface of any particular tissue, uh, that the immune system is then directed to, so that part of the immune system, uh, is directed and causes problems. But in a very real sense, it is your innate immune system going awry. It's, so it's auto in that it's contained within you and it's certainly an immune issue. Importantly though, and we'll, we should open this up later on.

• 23:05Gary Brecka?

  Yeah.

• 23:06Speaker 00

  I think in our third hour, maybe in the fourth.

• 23:08Gary Brecka?

  Yeah.

• 23:08Speaker 00

  We'll get there. You're in for a long.

• 23:10Gary Brecka?

  We still got to go back to brain brain, so that was 2013.

• 23:12Speaker 00

  I know. I was picking up from there.

• 23:14Gary Brecka?

  Yeah.

• 23:14Speaker 00

  But it's, it's interesting to me, and then I'll get back to my point, that, um, this explains brain brain. Cause when I wrote brain brain, it was about the correlations between elevated blood sugar, elevated A1C, dietary issues, and risk for Alzheimer's. Got that, but I didn't know how it happened. I didn't know why.

• 23:33Gary Brecka?

  Mechanistically, yeah.

• 23:34Speaker 00

  Mechanistically, now we get it. Now it all comes together. And I'm grateful at 71, finally the pieces came together. I wrote a book years later, several years later called Brain Maker, and I, I had the conclusion, strange as it may be, that there's a relationship between, get ready for this, gut health and brain health. I know, the, the gut-brain connection. So talked about that and.

• 23:56Gary Brecka?

  I read that too, yeah.

• 23:57Speaker 00

  Similarly, you know, there was a lot of pushback, but anyway, explains that too, because part two of our story away from immunometabolism is the effect of inflammation from anywhere in the body on polarizing these microglial cells away from being brain defending, supportive, to being the evil twin, to being destructive. Inflammation, the molecules of inflammation called inflammatory cytokines can come from the lungs when we're breathing PM 2.5s from wildfire smoke, uh, can come from a leaky gut because of dysbiosis or changes in our gut bacteria, can absolutely come from the mouth, uh, when we have periodontal disease.

• 24:40Gary Brecka?

  Oh, yeah.

• 24:41Speaker 00

  A powerful risk factor for Alzheimer's, why does that happen? Now we understand.

• 24:46Gary Brecka?

  The dental carries.

• 24:47Speaker 00

  You bet.

• 24:48Gary Brecka?

  Yeah.

• 24:48Speaker 00

  Not as much as the carries, as the periodontal disease, the gum disease carries as well. I mean, it's an, it's just another indication of poor dental health. So while we now understand all of these relationships, the empowering part is, okay, we'll talk about what we should be doing for people's dental health and gut health, and reducing your exposure to PM 2.5s by virtue of the fact that you're breathing 20,000 times in 24 hours, maybe we should pay attention to the quality of that air. We had a long discussion about what you're doing right here, uh, earlier, and, you know, hats off to you for doing that. We do the same thing.

• 25:26Gary Brecka?

  Yeah.

• 25:26Speaker 00

  It's, it's that important. I mean, you're paying attention to the quality of your water, air, especially these days, you know as well as I what's going on, uh, certainly in North America.

• 25:35Gary Brecka?

  Water is scary.

• 25:36Speaker 00

  Well, no, in air quality with respect to wildfire smoke and in Europe as well.

• 25:40Gary Brecka?

  Hmm. Wildfire smoke, I mean, lumina, um, I haven't tested the air in quite a while, but I tested the Miami day water and, you know, everybody talks about the fluoride, the chlorine. It was all of the PFAs and the other things that I found in there, um, heavy metals, pharmaceuticals, uh, that just made me really freak out and, and saw really aggressive water filtration.

• 26:03Speaker 00

  I'm not going to say that's a broad stroke, but I'm not going to, uh, play it down either. It's really important.

• 26:09Gary Brecka?

  Hmm.

• 26:10Speaker 00

  Uh, you know, the goal for me is if we can get people even a few onramps, here's what a better brain diet looks like.

• 26:18Gary Brecka?

  Yeah, this is, this is exactly where I want to go.

• 26:20Speaker 00

  Here's why you need to get.

• 26:20Gary Brecka?

  Take out a pen, guys.

• 26:21Speaker 00

  Yeah. Get some quality sleep tonight and moving forward. Here's why you absolutely.

• 26:27Gary Brecka?

  I had 100% sleep score last night.

• 26:29Speaker 00

  Oh, did you? You showed me that, yeah. I showed you my HRV, I was proud of that.

• 26:32Gary Brecka?

  Yeah, 70 HRV, that's.

• 26:34Speaker 00

  Yeah.

• 26:34Gary Brecka?

  Incredible. Be 70 years old.

• 26:35Speaker 00

  That's one year less than my age.

• 26:38Gary Brecka?

  Yeah.

• 26:38Speaker 00

  It's great. You know, they should say, uh, if you're a golfer, you should golf your age. I don't, I'm not a golfer, but you're, I wonder how it relates to HRV. But, uh, you know, the point is that, uh, these are powerful inroads to recharging your brain's destiny. And the idea that, uh, exercise, yeah, you want to be pumped up, you want to look good, you want to feel great, you want to sleep better, it's why exercise, yeah, all those things, but it's one of the most powerful tonics for brain health. There are hacks left, right, and center, and some of them have great merit. We talk about them in the book. You know, what's the, the future of, uh, would rapamycin be something that's in a brain healthy program? What about metformin? What about red light therapy? What about hyperbarics?

• 27:22Speaker 00

  Uh, there, well, we can talk about those things, but the broad strokes are what we've just mentioned, and do them, you've got to do them because.

• 27:30Gary Brecka?

  Exercise.

• 27:31Speaker 00

  Yeah.

• 27:31Gary Brecka?

  And in particular, any type of exercise, weight training, uh.

• 27:36Speaker 00

  I will say that, uh, uh, you know, the, the most important part is getting started.

• 27:42Gary Brecka?

  Yeah.

• 27:42Speaker 00

  But, you know, that's, it's, it's often, uh, a question of, well, which is better for my brain? Is it the aerobic part or the resistance training? And there was recently published a meta-analysis of 32 different studies, encompassed, encompassed thousands of patients, uh, and evaluated what was the cognitive outcome in individuals based upon if they were dedicated to the aerobics program? Whether it involved a, a dedicated aerobic program or doing aerobic exercise by playing pickleball or whatever it would be? Or those who did resistance training, weights, tension bands, machines, or even those who decided to do both. And by far and away, the winner was both.

• 28:22Gary Brecka?

  Really?

• 28:23Speaker 00

  Absolutely. And it makes sense now that, you know, you read their conclusion and why, but you think about it a little bit and, and we'll, we'll unpack that a little bit. But I just want to say, and we talked about this at lunch, um, that I want to add to that, okay, people are going to do, well, I do the rubbish, I do whatever, uh, resistance, but flexibility.

• 28:42Gary Brecka?

  Flexibility.

• 28:42Speaker 00

  And balance. Why? So you don't get injured.

• 28:45Gary Brecka?

  Those are the two, I would say, probably my weakest points. You know, I'm not very flexible and I never do any balance work.

• 28:53Speaker 00

  Yeah.

• 28:53Gary Brecka?

  Per se.

• 28:55Speaker 00

  But your wife has great balance.

• 28:56Gary Brecka?

  She has amazing balance.

• 28:57Speaker 00

  I know, but you can train balance.

• 28:59Gary Brecka?

  Hmm.

• 29:00Speaker 00

  And the reason you want to train balance is so you don't fall.

• 29:02Gary Brecka?

  Okay.

• 29:03Speaker 00

  And you're not thinking about it right now, but at.

• 29:05Gary Brecka?

  No, my dad's broken an arm and a hip.

• 29:08Speaker 00

  Yeah.

• 29:09Gary Brecka?

  In the last year.

• 29:10Speaker 00

  And, uh.

• 29:10Gary Brecka?

  In my house.

• 29:10Speaker 00

  People at, in my age category, I'll leave it at that.

• 29:13Gary Brecka?

  Yeah.

• 29:14Speaker 00

  Fall and, uh, may not know how to fall. First of all, and, and fall because they don't have good balance.

• 29:20Gary Brecka?

  Hmm.

• 29:22Speaker 00

  I don't know that you can train people how to fall, that's something you learn earlier in life.

• 29:26Gary Brecka?

  Yeah.

• 29:26Speaker 00

  Various things you can do where you learn how to fall, uh, cause I, I used to fall not frequently, but on occasion when I was running, uh, and there's ways of falling and you can not get hurt.

• 29:38Gary Brecka?

  Rolling over.

• 29:38Speaker 00

  Yeah, yeah.

• 29:41Speaker 00

  I fell once in front of, this is not part of our talk, but anyway, in front of a large crowd in Washington DC, I was actually invited to speak to the International Monetary Fund about the health implications of Alzheimer's moving forward. And guess what? It's a preventable, largely preventable situation. And I took a dive. There was a huge crowd.

• 30:00Gary Brecka?

  In front of the audience?

• 30:01Speaker 00

  No, no.

• 30:02Gary Brecka?

  Going up?

• 30:02Speaker 00

  Other audience that I think in front of one of the sites there. And I was really, you know, going fast. I was training for a marathon, I think at the time. And I took a terrible dive, but I rolled and I got up on my feet. There's a scene in Pee Wee Herman's Great Adventure where he crashes his bike, gets back on, he says, "I meant to do that. I didn't say I meant to do that."

• 30:23Gary Brecka?

  Yeah, that would have been-

• 30:24Speaker 00

  But I was thinking that.

• 30:24Gary Brecka?

  That would have been like sticking the landing, you know?

• 30:26Speaker 00

  Oh, I know.

• 30:27Gary Brecka?

  Threw your hands up.

• 30:28Speaker 00

  It's true. When you mess up, if you can pull it off, uh, yeah.

• 30:31Gary Brecka?

  Yeah, if you actually get points. So those are probably, that's probably from your karate days, you know? Cause you learn that, uh, how to tuck your head and kind of roll it onto your shoulder.

• 30:40Speaker 00

  Yeah, there's other, I think judo teaches you more how to fall.

• 30:43Gary Brecka?

  Yeah.

• 30:44Speaker 00

  But yeah, various martial arts will teach you how to fall. I think learning how to fall is a pretty darn good skill to have.

• 30:49Gary Brecka?

  No.

• 30:50Speaker 00

  And, uh, people don't really train that, but you know, when you're a kid, you're always falling down and, and you either get hurt or you're not. So you learn pretty quickly.

• 30:57Gary Brecka?

  Yeah.

• 30:57Speaker 00

  Football teaches you how to fall too. Tackle football.

• 31:00Gary Brecka?

  Okay. So, um, aside from tackle football, so strength training and, and obviously aerobic training on a consistent basis, over a prolonged period of time.

• 31:09Speaker 00

  Let me finish that thought though, in that, uh, sorry to interrupt you. But in that study, the people who derived the best benefit were those who had already cognitive impairment to some degree, and also the group 65 years and older. So you're just about to ask me, is it ever too late?

• 31:25Gary Brecka?

  Right.

• 31:25Speaker 00

  It is absolutely not ever too late.

• 31:28Gary Brecka?

  Hmm. So starting a, a strength and resistance training program now with some flexibility and balance moved in and some cardio component, uh, and doing that consistently, minimum three days a week.

• 31:40Speaker 00

  That's right. And, you know, calling it like it is, losing muscle mass is a very big risk factor for metabolic issues, therefore directly related to Alzheimer's and cardiovascular disease, but also directly related to risk for Alzheimer's, losing muscle mass called sarcopenia.

• 31:56Gary Brecka?

  Wow.

• 31:57Speaker 00

  And I'm, I tell you, N of one, and not that, uh, there's not plenty of data that, uh, supports this. The older you get, the harder it is to keep muscle mass.

• 32:06Gary Brecka?

  Hmm.

• 32:06Speaker 00

  You have to work harder.

• 32:07Gary Brecka?

  Yeah.

• 32:08Speaker 00

  It's more time, it's paying attention to adding creatine to your regimen, testosterone perhaps to your regimen, all of the things that you've talked about on the podcast, you've interviewed the experts. It all makes incredible sense.

• 32:21Gary Brecka?

  So you're a fan of creatine?

• 32:23Speaker 00

  I am.

• 32:23Gary Brecka?

  I actually, that was one of the areas I wanted to talk to you about with, with, um, you know, there's some big claims out there around, uh, creatine. I was curious what you felt the data supported in terms of cognitive function, crossing the blood brain barrier, mitigating sleep deprivation, um, those, those kinds of things with creatine.

• 32:43Speaker 00

  So let's unpack that a little bit. The, the systemic creatine that you have doesn't really make its way to the brain to any significant degree. It does, uh, but the brain makes its own creatine. Uh, the creatine that's manufactured in the liver and the kidneys works for the rest of your body, definitely works for your muscles. And that sort of is this relationship that we're trying to take advantage of. If you can raise your blood level of creatine, though it may not make its way fully to the brain, you're supporting muscle growth and that's what you want to support your brain. Why? Because your muscles are an endocrine gland. We, you know, we get, begin to get our arms around that. What is that all about?

• 33:24Gary Brecka?

  Like a glucose sponge.

• 33:25Speaker 00

  Well, not just that, but you know, the definition of the endocrine gland, the thyroid, the pituitary, the adrenals, is that these are organs that make chemicals that go elsewhere and do other things. You know, there are thyroid receptors on all of your tissues. Uh, the adrenals stimulate, you know, various tissues, uh, during times of stress. That's one part of the adrenal and pituitary certainly has effects throughout the body. Uh, the muscles do exactly the same thing. They create chemicals that have a huge impact on our metabolism, on regulation of our blood sugar. Uh, and even, um, irisin, one of those myokines, myo muscle kind moves.

• 34:07Speaker 00

  Uh, irisin being one of those chemicals makes its way to the brain and stimulates the production of something called brain derived neurotrophic factor. We talked about it earlier before we went on, on, uh, camera. That is something we want to have as much of as possible because it amplifies the growth of new neurons, amplifies the formation of synapses. So our neurons can talk to each other and is generally just a good player in the brain. So the more of that, the better. We bring that about by exercising. So who wouldn't want to do that? Other things input to BDNF as well. There are some research protocols to increase BDNF

• 34:49Speaker 00

  with various interventions, but even omega threes, DHA in particular amps up, uh, BDNF production. So this isn't a direct effect of muscle activity to the brain. It's an intermediary effect of this irisin chemical produced by muscles making its way to the brain.

• 35:10Gary Brecka?

  Hmm.

• 35:11Speaker 00

  Uh, interleukin six, uh, which we've been saying for years, oh, that's a bad inflammatory cytokine made when muscles are active. And in some ways it is a bit pro-inflammatory, which is probably a good thing as it relates to exercise. We need a little, a little inflammation.

• 35:26Gary Brecka?

  Sure.

• 35:27Speaker 00

  As a hormetic stress to amplify recovery and repair. But that said, this interleukin six cytokine is actually the key for how muscle activity stimulates something called AMP kinase. Now I don't want to be too technical about all of this.

• 35:43Gary Brecka?

  AMPK.

• 35:44Speaker 00

  But AMPK is a powerful target for our mitochondria, allows the mitochondria to be removed if they're defective. It amplifies mitochondrial biogenesis, the growth of new energy producers, the mitochondria, through activation of something called the PG, uh, PGC one alpha pathway. But the point is exercise through IL six, through AMP kinase, PGC one alpha is good for the mitochondria. Let's just say exercise then connects to mitochondria.

• 36:15Gary Brecka?

  That, that, that hormetic stress causes mitochondria to improve its metabolic function and potentially even increases mitochondrial density, right? The proliferation of-

• 36:24Speaker 00

  It absolutely does. And how can we see that? You can actually visualize that. It's when, uh, the normal fat gets converted into brown fat. The metabolically favorable kind of fat.

• 36:37Gary Brecka?

  The thermostat.

• 36:38Speaker 00

  And it's brown because it has more mitochondria.

• 36:41Gary Brecka?

  Ah, that's why it's brown. I knew it had more mitochondria.

• 36:45Speaker 00

  That's why it's brown. Cause so rich in mitochondria. But let, let me rein this back to, uh, our time together today.

• 36:51Gary Brecka?

  Yeah.

• 36:52Speaker 00

  Uh, which I'm really enjoying.

• 36:54Gary Brecka?

  Yeah, I am too. I really am.

• 36:55Speaker 00

  Yeah, we hadn't, we knew each other kind of perfectly, but, uh, anyway, um, and that is that the shift of these microglial cells from being supportive to being destructive, from being brain defenders to being brain destroyers is characterized by a shift in their mitochondrial function.

• 37:17Gary Brecka?

  Hmm.

• 37:18Speaker 00

  When the, the shift happens, their mitochondrial function basically evaporates almost fully. Now they're using glycolysis, another energy producing pathway, far less effect. And interestingly, uh, that what cancer cells use, we talked about that in the hallway.

• 37:34Gary Brecka?

  Glycolic respiration.

• 37:36Speaker 00

  They're using a, a far less efficient way of making these ATP energy molecules. So everything that we have talked about, about exercise in the mitochondria just now, AMP kinase and all of that, and that we will talk about that deals with mitochondria. The play here is that when you improve mitochondrial function, you're protecting the supportive brain defender, microglia in your brain. Let me tell you how vast this becomes. I mentioned earlier laundry list of neurodegenerative conditions that are characterized by this shift of the mitochondria away from being supportive to being destructive.

• 38:18Gary Brecka?

  Which is the hallmark shift of these microglial cells going from being reparative to destructive.

• 38:25Speaker 00

  Exactly.

• 38:25Gary Brecka?

  Okay.

• 38:26Speaker 00

  We can image that in living humans now.

• 38:29Gary Brecka?

  In the brain?

• 38:30Speaker 00

  In the brain. We can absolutely do scans.

• 38:33Gary Brecka?

  Is that a Q E E G?

• 38:34Speaker 00

  Nope. Uh, it's called a TSPO scan. And TSPO is a marker that is much more expressed on the mitochondrial membrane of the M1 damaging microglial cells in comparison to the supportive microglial cells. So when you do a TSPO scan of an individual, if it lights up, it's telling you those microglia have shifted. And in my, in my lectures, I show what a normal brain versus an Alzheimer's brain, TSPO scan looks like. Let's look at that image right now.

• 39:08Gary Brecka?

  Yeah, yeah.

• 39:09Speaker 00

  And

• 39:10Gary Brecka?

  So walk us through what they're seeing right now.

• 39:11Speaker 00

  You see on the left side of your screen, what you're seeing right now is the normal brain. On the right side of your, of the image, that's the TSPO image in the Alzheimer's brain. It's light up. What you're seeing light up here is evidence of the microglia being activated into their destructive condition. And what you're actually imaging is this TSPO binding to a unique receptor on the surface of the mitochondria of these activated microglial cells. Let's look at this next slide, because I think it's really compelling.

• 39:43Gary Brecka?

  Okay.

• 39:44Speaker 00

  What we're seeing here is a list of all of the neurodegenerative and other conditions in which TSPO imaging is positive. Meaning, if you look at this list, these are all diseases and disease states in which the microglia have shifted to becoming destructive.

• 40:04Gary Brecka?

  Wow.

• 40:05Speaker 00

  Microglia shifting to becoming destructive is something that we now have the tools to target. And most importantly, we should be living our lives, choosing lifestyle interventions such that we can keep our microglia away from being this TSPO image type of situation where they're shifted already to being destructive. We have the tools to make that happen right now.

• 40:29Gary Brecka?

  Hmm. What are the tools once you are in that situation? Because a lot of what we've talked about is what we do to prevent that situation. Exercise, controlling blood sugar, getting, you know, making sure that you don't become insulin resistant and to the extent that you are managing insulin resistance. Omega three, high omega three, fatty acid intake. I would imagine a diet, a lower glycemic diet. But now that we find ourselves in a situation like I'm in with my parent, where I haven't done that image, but I assumed that it would light up. I've seen the hypoactive areas of the brain on

• 41:10Gary Brecka?

  Q E E G. And so what do we do now to try to restore that access? Because one of the fascinating things that we talked about before the podcast was that even in these conditions like Alzheimer's, patients are not losing their memory per se, they're losing access to their memory. How do we restore access? Or can we?

• 41:33Speaker 00

  Well, we give you the tools, and I will walk you through it, but

• 41:37Gary Brecka?

  Yeah.

• 41:38Speaker 00

  Far be it from me just to sit here and say, well, this is what I think we should do. Let's talk about a study that was published last year in the Journal of Prevention of Alzheimer's. Actually, no, that's not worth publishing, but it was published by, we'll cover that study in just a moment, because I think it's really very relevant. This study was carried out by Dr. Rudolph Tanzi at Harvard, along with Dr. Dean Ornish, an interventional trial on 51 patients who were diagnosed with Alzheimer's disease. A, an intervention that lasted around 20 weeks. What did they do?

• 42:13Gary Brecka?

  Yes.

• 42:14Speaker 00

  They changed their diets, they increased their exercise, they managed their stress. And what did they find?

• 42:21Gary Brecka?

  Well, that's it. Changed their diet.

• 42:23Speaker 00

  Increased exercise, manage stress.

• 42:25Gary Brecka?

  Right.

• 42:26Speaker 00

  Okay. Normally, in 20 weeks, Alzheimer's patients decline. In 20 weeks, Alzheimer's patients on the newer beta amyloid drugs decline. And we're going to talk about that, because it's really, it's fundamental, I think, to this whole discussion that these drugs are ineffective. We'll talk about that.

• 42:48Gary Brecka?

  They're focused on the endpoints, like the

• 42:51Speaker 00

  Neurofibular tumors.

• 42:52Gary Brecka?

  Exactly right, which is the beta amyloid, which is unfair. We'll get there.

• 42:56Speaker 00

  Right.

• 42:57Gary Brecka?

  I have a few things to say about that.

• 42:58Speaker 00

  Yeah.

• 42:59Gary Brecka?

  That's true.

• 43:00Speaker 00

  I know you do. But what they found is that in 70% of the individuals that underwent this intervention, their cognitive decline either stopped, which no drug can do, or improved. Their cognitive function improved.

• 43:18Gary Brecka?

  Hmm.

• 43:19Speaker 00

  I want that one to stew for a moment, because most of your, of your audience has not heard of that study, and they should have. Most of your audience has heard about the idea of, oh, we've got a brand new drug that targets beta amyloid for mom or dad when they start to have cognitive impairment. And we'll talk about, no, I'm going to talk about that.

• 43:37Gary Brecka?

  Right.

• 43:37Speaker 00

  But I think that was, it was very telling. It was a small study. Granted, it was a small study. But let's wind the clock back a little bit to individuals who are at risk because of their metabolic issues, a much larger study published in the Journal of the American Medical Association. And it was called, is called, the Pointer Study that was completed last year. This was more than 20,000 people, a two-year intervention where they did the diet, the exercise, the stress mitigation, and had them doing cognitive training, using a particular app, Brain HQ. They had two arms. One arm got these recommendations

• 44:18Speaker 00

  and did these, this type of training, but had very aggressive interaction with people in the study. During the two-year study, 18 times per year, 36 total, meetings virtually or in person, how are you doing? What's the diet like? How's the exercise coming along? The other arm had the same program.

• 44:36Gary Brecka?

  I mentioned these were older ages, right?

• 44:38Speaker 00

  That's an important point.

• 44:39Gary Brecka?

  So a lot were deconditioned.

• 44:40Speaker 00

  Well, not just deconditioned, but these were people selected because they were at risk for, for Alzheimer's because they are metabolically compromised, cardiovascular disease, overweight, age 65 and older.

• 44:53Gary Brecka?

  Okay.

• 44:54Speaker 00

  So they're already set up for Alzheimer's. They are, they're well on the continuum. So the other arm didn't get the, the handholding, if you will, the 36, they got a total of three a year, so a total of six meetings with people. How's it going? Are you doing the program? So they pretty well got the program and almost do your best, and we'll talk to you later. The end of the program, they evaluated these individuals with cognitive assessment. And these people are expected to decline cognitively because of their age, because of their metabolic derangement, if you will. No, they didn't. They didn't even stabilize, but they dramatically improved across various domains.

• 45:37Gary Brecka?

  Wow.

• 45:37Speaker 00

  Now, that's what they found in the group that had the handholding, the deep intervention. But here's the part of the Pointer Study that I want people to Google it, find it, Pointer Study, JAMA, you'll find it, is that the group that got the program and didn't really get the guidance, had a fairly dramatic improvement in cognitive function as well. Not the extent of the other group, but nonetheless, an improvement when they should have declined.

• 46:05Gary Brecka?

  Wow.

• 46:05Speaker 00

  That's how I answer your question about, is it too late? Is it reversible? And what can we do? You know, it's about doing these things, though, earlier, get these things involved earlier in someone's life, so it's not as challenging.

• 46:20Gary Brecka?

  You know, I'm all about optimizing performance. And lately, I've been using the Ion Weighted Vest during my workouts, and it's been a game changer. It isn't your average weighted vest. It's designed to fit like a second skin, activating your core, improving blood flow, and even helping you with recovery while you train. What I love most is that the weight is perfectly distributed. It doesn't pull on your shoulders or throw off your alignment. Whether I'm doing strength training, or cardio, or just taking a walk, I'm burning more calories, building muscle, and pushing my endurance even further. If you're serious about leveling up your training and unlocking your full potential, check out the Ion Weighted Vest at iongear.com. That's A I O N gear.com. And you can use code ULTIMATE

• 47:04Gary Brecka?

  for 10% off and start training smarter today. Now, let's get back to the Ultimate Human Podcast. So just being more specific, what were the dietary interventions? I assume removing highly processed foods, lowering the glycemic impact of, of high glycemic sugars.

• 47:21Speaker 00

  Yeah. And it, we'll talk about that.

• 47:23Gary Brecka?

  Was there a keto reset, something like that?

• 47:25Speaker 00

  No.

• 47:26Gary Brecka?

  No.

• 47:26Speaker 00

  But again, back to Benjamin Franklin, it is a question of, well, well done is better than well said.

• 47:35Gary Brecka?

  Right.

• 47:36Speaker 00

  Or well said, I think he said, well said is not as good as well done. You got to do it.

• 47:39Gary Brecka?

  Right.

• 47:40Speaker 00

  And again, you know, as Kennedy said, the time to fix a roof is when the sun is shining. And that's what we really want to target. It can be done later on, as I just demonstrated. So the, the diet in the interventional trial from Rudolph Tanzi and Dean Ornish was very much a plant forward, plant centric diet.

• 48:01Gary Brecka?

  Okay.

• 48:02Speaker 00

  That's been Dr. Ornish's push for cardiovascular disease, or cardiometabolic disease for an awful long time. I, I use the term cardiometabolic because metabolism affects the heart. Well, metabolism affects everything. So we'll say neuro metabolic disease as well. That's what Alzheimer's is. This may be the first time I've ever said that term, neuro metabolic disease.

• 48:25Gary Brecka?

  Yeah.

• 48:26Speaker 00

  I think it is, but let's make that stick, because

• 48:28Gary Brecka?

  Yeah, let's make that stick.

• 48:29Speaker 00

  I don't even think I put it in the book.

• 48:30Gary Brecka?

  We'll coin it here today.

• 48:31Speaker 00

  Yeah.

• 48:34Speaker 00

  Can you guys get me neurometabolicurl.com? No, I'm kidding.

• 48:39Gary Brecka?

  Neuro metabolic url.com.

• 48:42Speaker 00

  But, but, you know, the point is that these are all ultimately metabolic issues, and through the intermediary of immunity, now immunometabolism, disease manifests. Cardiovascular disease is primarily an immune related issue. What's narrowing the coronary arteries is an immune response. When you take the plaque out of a carotid artery or a coronary artery, it's loaded with immune cells. So it's an immune response, very much so, directed by free radical mediated stress and inflammation. So to get, to get back to where we were, that these lifestyle interventions are by mainstream standards, not really embraced, and often

• 49:24Speaker 00

  derogated. But when we look at the peer reviewed literature, it's incredibly supportive. In the world of neurology, This is our only answer right now. Am I gonna keep the door open and welcome an Alzheimer's drug? If it does two things, it's fairly safe and it does the job. Absolutely. I am so down for that. I will embrace that with open arms. We don't have anything like that right now. Despite the TV commercials to the general population. And despite the ads that are appearing in my neurology journal as a neurologist. That I should be recommending these drugs that target beta amyloid.

• 50:08Speaker 00

  I went into it in great depth in this book. Again, coming from somebody who would absolutely 100% be so down for these drugs.

• 50:17Gary Brecka?

  Yeah.

• 50:17Speaker 00

  I'm all for making the toolkit bigger. But fundamentally, we have to practice under two principles. Number one, primum non noser, above all, do no harm.

• 50:27Gary Brecka?

  Yes.

• 50:28Speaker 00

  And number two, looking at the risk benefit ratio. These drugs that are being used have dramatic risk. And the benefit is nil. A Cochrane analysis was published about three months ago. The gold standard, you would agree, in looking at trying to answer a question. The question that was asked, are these drugs doing anything?

• 50:52Gary Brecka?

  Right.

• 50:53Speaker 00

  And here's the answer. They, they, they looked at 20,342 individuals who were in 17 different studies. Each study lasting 18 months of the current round of amyloid digesting proteins, if you will, or monoclonal antibodies that take beta amyloid out of the brain as a treatment for Alzheimer's. What did they find? Risk. 25% of people getting these IV drugs to rid their brains of beta amyloid had brain hemorrhages, brain swelling, or died.

• 51:29Gary Brecka?

  Wow.

• 51:29Speaker 00

  That's what?

• 51:30Gary Brecka?

  25%?

• 51:31Speaker 00

  25, one in four.

• 51:33Gary Brecka?

  Wow.

• 51:34Speaker 00

  Number two, okay, that's the risk. I'm not making this up. I wish I were making this up. Then people could write comments about, oh, Gary Brek had this case, this guest, whatever. I'm not making it up. I wish I were, because then we could challenge veracity. Challenge my veracity. What's the benefit? The conclusion was basically none. The word used in the Cochrane analysis was the benefits were trivial. Now, I say that and present this information in juxtaposition to the study that I quoted to you from Dr. Rudolph Tanzi at Harvard. Where they changed the lifestyle. And the, the downsides or the side effects were

• 52:17Speaker 00

  that people's blood sugars came down, they lost weight, they felt better. And that was the, that was the other things that happened.

• 52:25Gary Brecka?

  Right.

• 52:26Speaker 00

  And they're, these are existing Alzheimer's patients. Back to the Pointer study that helps clarify one other point that you asked. These are the metabolically compromised 65 year olds who had a two-year intervention of lifestyle plus brain training.

• 52:44Speaker 00

  I want to make it clear that a significant number of these individuals carried the APOE4 risk marker for Alzheimer's.

• 52:54Gary Brecka?

  Predisposed. And what does that gene? What is the line that predisposes you to Alzheimer's? What does that gene do or not do that predisposes you to?

• 53:04Speaker 00

  I didn't, I didn't write you that question ahead of time. I should have though, because it's a great question. Fundamentally, it, it threatens the microglial cells.

• 53:15Gary Brecka?

  That's what it does.

• 53:15Speaker 00

  Fundamentally, and more so in women than in men.

• 53:18Gary Brecka?

  So it leaves you, you are more likely because of this gene snip to have microglial cells who shift their metabolism and become villainous rather than become helpers.

• 53:28Speaker 00

  That's right. And again, to use your words earlier, it's a predisposition. It's not a genetic determinant.

• 53:36Gary Brecka?

  Yeah. It's the epigenetic factors that clearly are emerging.

• 53:39Speaker 00

  Increased risk. Yes, it is. So you need to ratchet it up. If you have been told you carry the APOE4 allele, then by all means, pay heed to what we're saying today. Because it doesn't have to manifest at all. And, you know, it's interesting because it kind of talk, it gets us back to the beta amyloid hypothesis, which is only a hypothesis, which I think made it, made people believe that that is the cause of Alzheimer's. Get rid of the beta amyloid, problem solved. It didn't work. Still isn't working.

• 54:11Gary Brecka?

  Right.

• 54:12Speaker 00

  But, you know, to be fair, there are plenty of people who have been demonstrated to have high levels of beta amyloid in their brains and are cognitively intact, thank you very much.

• 54:22Gary Brecka?

  I was just reading that.

• 54:22Speaker 00

  And others who have no significant amounts of beta amyloid and are going down the tubes with respect to Alzheimer's as a diagnosis. So that is by all means, not the story and we need to move ahead. And really abandon this hypothesis. And where the research is now and where it's going in the future is targeting the microglial cells. I mean, you know, some very high level work is being done to create monoclonal antibodies. That there's a study at Brigham and William, Brigham and Williams using a particular monoclonal antibody, this is a very high level science that's given now intranasally that helps keep the microglia

• 55:08Speaker 00

  in their M2 supportive configuration. They're exploring that in multiple sclerosis and in brain trauma. I describe it in the book. There are ways of targeting the mitochondria. Think back to our conversation that a major characterization of the shift from being supportive to being destructive is a loss of mitochondrial function. There's a product that's called RNS60 that definitely targets mitochondria. It's a proprietary way that saline solution is hyperoxygenated, creating these nano bubbles of oxygen that seemingly mitochondria love. There's a future there. Even the drug metformin has a mitochondrial play.

• 55:51Gary Brecka?

  So there's a Not just from its glucophage.

• 55:54Speaker 00

  It is glucophage. But there, there's much more than simply the activation of the AMP kinase that it looks like metformin glucophage is doing. So there's a lot of interest, you know, we will watch very closely the arms of the TAME trial. Once that is completed to look at what people taking metformin are gaining, if they're gaining anything, and they will, based upon this way of targeting their mitochondria. But guess what? You've got incredibly powerful tools for targeting your mitochondria right now. And it's more of a ketogenic diet and exercise. That's one of the most powerful ways of targeting your epigenome.

• 56:38Speaker 00

  Targeting your epigenetics, but also targeting mitochondrial.

• 56:41Gary Brecka?

  So even if they're a little deconditioned, getting them to do, you know, like my, my mother can't go out and get into zone two cardio, run in a 5K.

• 56:51Speaker 00

  But she can walk to the mailbox.

• 56:52Gary Brecka?

  She can walk, she can definitely walk to the

• 56:53Speaker 00

  Tomorrow, she can do that twice.

• 56:55Gary Brecka?

  Yeah. That she could definitely do. And she could do resistance training. She's very strong.

• 56:59Speaker 00

  Your mother may surprise you.

• 57:00Gary Brecka?

  Yeah.

• 57:01Speaker 00

  You may surprise you. I, I could imagine in a couple of years, as her cognitive function improves, that you might be well surprised at what she's able to do physically.

• 57:11Gary Brecka?

  Well, so the exercise, obviously, the glycemic diet, the omega threes.

• 57:18Gary Brecka?

  I, I think it's also important that we touch on the importance of sleep and the glymphatic system and what's happening with the glymphatic system during deep phases of sleep. And how important

• 57:29Gary Brecka?

  getting proper sleep and how detrimental sleep deprivation, at least over a prolonged period of time, short bouts, you know, yeah, travel or what have you, but.

• 57:37Speaker 00

  What can I say? It's huge. It is, it is, it's huge. Sleep, eat, and exercise.

• 57:45Gary Brecka?

  Yeah.

• 57:46Speaker 00

  What, what was it? Eat, pray, and love. Important as well, but, yeah. And, and sleep might be clearly the most important of all three. Diet's not great, exercise not often. You don't sleep, oh, you're done. You are finished. Even, you know, if you don't sleep for a, for a few days, you won't survive.

• 58:08Gary Brecka?

  Yeah.

• 58:09Speaker 00

  You can fast for, I mean, you know, people fast.

• 58:12Gary Brecka?

  30 days.

• 58:12Speaker 00

  Oh, yeah.

• 58:13Gary Brecka?

  Yeah.

• 58:14Speaker 00

  So we have that ability and

• 58:17Gary Brecka?

  Now, sleep deprivation is the old, one of the oldest forms of torture. I mean,

• 58:21Speaker 00

  That's right. That's, you know, your brain just degenerates very quickly. Mechanistically, what's happening, you mentioned the glymphatic system, we can unpack that certainly.

• 58:30Gary Brecka?

  I love it.

• 58:31Speaker 00

  Sleep is hugely influential in terms of inflammation, in terms of insulin functionality and overall metabolic regulation. Those are the keys to the kingdom in terms of regulating your microglial cells. Keeping them supportive or allowing them to become destructive. That's the keys to the kingdom right there. So

• 58:55Speaker 00

  even one night's non-reversive sleep dramatically affects insulin functionality. Is manifested by elevation of your blood sugar compared to the baseline. Ramps up the production of these inflammatory cytokines that your microglia will see. Tend to shift them to the dark side, as it were. And generally is to be avoided. It happens. Even cognitively, that very next day, you're having issues.

• 59:21Gary Brecka?

  Yes, we all know.

• 59:21Speaker 00

  Interestingly, a study came out this year that showed that to some degree, some of the cognitive dysfunction that you have after one night of not sleeping or not sleeping enough or well enough is offset by caffeine.

• 59:37Speaker 00

  I mean, well, we all inherently knew that.

• 59:39Gary Brecka?

  Yeah, yeah.

• 59:40Speaker 00

  Best practice here. But this, this actually looked at what's going on and, and on cognitive testing. And I think it involved a FMRI evaluation as well. So, you know, underrated, you spend eight hours, you should, or thereabouts, sleeping. That's a third of your life.

• 59:57Gary Brecka?

  Yeah.

• 59:58Speaker 00

  Though you were spending more as an infant and a toddler. But a third of your adult life should be spent doing this. You're not going to sleep, you're not going to eat for eight hours or exercise for eight hours.

• 1:00:08Gary Brecka?

  Right.

• 1:00:08Speaker 00

  I guess some people might, but a third of your life, allowing your brain to contextualize your experience, to build new memories and to, via activation of the glymphatic system, help offload the debris that is accumulated, the misfolding of the proteins, the glycated proteins, the proteins that abound inappropriately to blood sugar and the bacterial breakdown products that your brain does in fact accumulate.

• 1:00:35Gary Brecka?

  Hmm. And, and where do you fall on creatine supplementation in older adults or specifically those with cognitive decline? Because we, we touched on it briefly, but do you have any opinions on the form of creatine? Monohydrate versus hydrochloride? Have you read the studies where it can mitigate the effects of sleep deprivation? And certainly in some cases, some wild claims about, I'm gonna say reversing Alzheimer's, but treating.

• 1:01:05Speaker 00

  Well, let me, let me just start with that. The study was extremely small and it was an interventional trial.

• 1:01:10Gary Brecka?

  Like an N of two or something, right?

• 1:01:12Speaker 00

  I think it was five.

• 1:01:13Gary Brecka?

  Five, okay.

• 1:01:14Speaker 00

  But it was a very small trial. And frankly, there were some cognitive improvements in these individuals. I mean, we need a big trial of, of creatine as it relates to Alzheimer's. And what they did demonstrate that I think was really quite remarkable is they were able to image creatine levels in the brains and in fact demonstrate that it increased. So we've got a way, a way to go, ways to go. But I would say that mechanistically, as we understand what creatine is able to do, it makes sense. It's, I recommend it. It's one of my key supplements in this book. And is it early for me to be bullish on creatine? Yep, it is. And I'm fully happy to admit that. Do I take it every single day? You bet I do. Do I take?

• 1:01:58Gary Brecka?

  How much do you take?

• 1:01:59Speaker 00

  I take about seven grams creatine monohydrate. I'm seeing the data on better GI tolerance and absorbability of creatine monohydrate, but I'm not compelled by it.

• 1:02:09Gary Brecka?

  You mean hydrochloride?

• 1:02:10Speaker 00

  Hydrochloride, yeah. That's correct. And so I'm not compelled by the idea that hydrochloride is necessarily dramatically better. We'll watch.

• 1:02:18Gary Brecka?

  More water soluble, I think, but.

• 1:02:19Speaker 00

  Yeah, yeah. And we'll watch that. But creatine monohydrate is widely available. It's really inexpensive. It's tasteless. Yeah, you can have GI upset if you overdo when you first start in. No question. But if it doesn't enhance mitochondrial function in the brain, which is what we're hoping for, but does allow you to perhaps build a little bit more muscle mass and enhance mitochondrial activity in the muscles, that's good enough for me.

• 1:02:47Gary Brecka?

  Right.

• 1:02:47Speaker 00

  Based upon our earlier conversation, the relationship between muscle mass and muscle activity and functionality, ultimately on the brain, through the formation of these myokines that are good for the brain and good for metabolism, then, then I am all in. The, the story is unfolding. I wanted the readers to be, go ahead and start your creatine with disclaimer, your healthcare overseeing all of this as if, well, hoping that your healthcare provider has heard of creatine, we'll leave it at that. But I don't think we're too early. Risk, I don't see much risk. I mean, there's been a discussion about people with existing kidney disease to check with your healthcare provider on the front end.

• 1:03:31Speaker 00

  And I think there's an argument that when you take creatine and you raise your levels, it's metabolic downstream manifestation is the formation of something called creatinine. So they're sounding similar, but they're very different. So your creatinine level actually may go up as you take creatine. Why is that relevant to this discussion of the kidney issue? Because when your creatinine level climbs, then your doctor might say, gee, that's an indication of kidney damage and your, you know, your kidney function is declining. Well, realistically, it's rising because you're taking a supplement that is metabolized into creatinine. So, yeah, it's worth looking at.

• 1:04:16Gary Brecka?

  I've seen that in you do blood draws on athletes that have just done a heavy squat workout.

• 1:04:22Speaker 00

  Yeah.

• 1:04:22Gary Brecka?

  They look like they're in kidney failure.

• 1:04:24Speaker 00

  Based on the blood work.

• 1:04:25Gary Brecka?

  Based on the blood work is what I mean. You know, because their creatinine's off the chart and.

• 1:04:28Speaker 00

  Exactly.

• 1:04:29Gary Brecka?

  So eight hours later, it's normalized.

• 1:04:31Speaker 00

  I mean, there are other ways of assessing kidney function. Let's look at the BUN.

• 1:04:34Gary Brecka?

  EGF.

• 1:04:35Speaker 00

  Let's look at the calculated glomerular filtration rate. You're correct. But to suddenly say, no, stop creatine, look, your creatine, creatinine went up.

• 1:04:46Speaker 00

  To be fair, I mean, maybe somebody is having renal issues for that reason or other reasons. I'm not saying just because you started creatine that you should ignore your other blood work. But, you know, that's what we need to think about. So let me just, you know, recognize that creatine in and of itself is perhaps not necessarily the mitochondrial tonic that I think it's made out to be. What creatine does is, is in the presence of an enzyme, phosphocreatine, or rather creatine phosphokinase, that creatine binds to phosphorus, holds on to that, rather binds

• 1:05:27Speaker 00

  to, creates a phosphate binding to creatine, forming phosphocreatine that then serves as a reservoir for that phosphate group to then participate in the formation of ATP when it's needed. So there's this, right in my next door neighbor's house is a great source for me to make energy. That's what phosphocreatine is. Well, it's right in, it's right in the garage in my ATP producer. So, you know, it's, it's a resource for better ATP production. So in that regard, that's, that's how it works.

• 1:06:02Gary Brecka?

  Hey guys, let me tell you about one of my favorite new hydration drinks. Now, this is for distance athletes, HIIT's cardio exercisers, people that sweat a lot or exercise intensely. And A Game is a hydration drink. It has eight essential vitamins. It has all of the electrolytes, the entire suite of B vitamins. Before you freak out and read that it has 21 grams of sugar, which it does, the sugar is coming from natural cane sugar and honey, my preferred mechanisms for getting glucose into the blood during intense exercise. It also has natural flavors, but these natural flavors don't come from bacterial fermentation. They actually come from real citrus fruits and the color is from vegetable juice, not artificial dyes. So next time you're looking for a great hydration drink and you're exercising intensely, A Game is your choice.

• 1:06:46Gary Brecka?

  Now let's get back to the Ultimate Human Podcast. In, in the book, do you talk about any other must have supplements or supplements that look promising for brain support? I mean, I think this whole wave of neurotropics and, you know, brain health supplements, you, you see they're becoming extremely popular.

• 1:07:10Gary Brecka?

  I, I wonder if you have an opinion on any of those or if you, are there any that are must haves in your book or any that you're excited about that are on the horizon for neurocognitive decline of all, of all sorts? And it specifically may be related to the microglial cells.

• 1:07:26Speaker 00

  Yeah. I will, I will put a huge vote in for vitamin D. Who knew?

• 1:07:33Gary Brecka?

  Great.

• 1:07:34Speaker 00

  It's, might be one of the cheapest supplements out there these days.

• 1:07:37Gary Brecka?

  Collocalciferol.

• 1:07:38Speaker 00

  Yeah. And why?

• 1:07:41Gary Brecka?

  It's the only vitamin that human beings make on our own. So you've got to think, wow, if we don't need to eat, drink or breathe to make vitamin D, you know, we just need some cholesterol and some sunlight.

• 1:07:52Speaker 00

  Cholesterol.

• 1:07:53Gary Brecka?

  I'm oversimplifying, but.

• 1:07:54Speaker 00

  No, that, that's pretty simplified.

• 1:07:56Gary Brecka?

  Basically what you need. You know, then it has to be pretty important to human function because we don't even need to get it from diet.

• 1:08:05Speaker 00

  There are vitamin D receptors on microglial cells. Let's start there.

• 1:08:10Gary Brecka?

  That's wild.

• 1:08:11Speaker 00

  And I'll backtrack a little bit because these days people are understanding their genetic profiles and learning that they may have polymorphisms or variations in their vitamin D receptors. So for all of you who get your genetic material printouts, look for changes in the VDR information, vitamin D receptors, and they'll give you whichever program you're on, whether it's three X four, whatever genome sequencing company you're working with, they'll tell you you have a VDR polymorphism and you might need to consider a higher dosage of vitamin D. Or as you well said, perhaps get a little bit more sunlight. Sunlight is a pretty effective way.

• 1:08:56Speaker 00

  But we wear clothes generally outside, most of us do, some of us don't, or some people don't. But, but that said, I, I don't want to say that everyone should take vitamin D as a supplement out of hand. Get your blood level checked.

• 1:09:13Gary Brecka?

  Right.

• 1:09:13Speaker 00

  If you're already between 60 and 80 on your, on your levels, then by all means you're doing great. Whatever you're doing seems to be working. Maybe you're getting your vitamin D from sunlight, from food, from your multivitamin or wherever. But if it's not, and I'm talking now to most of your, maybe not your audience, but most of the general population.

• 1:09:32Gary Brecka?

  More than 50%.

• 1:09:33Speaker 00

  Yeah. Your vitamin D is not, though it may be considered borderline normal range, it's not optimized.

• 1:09:39Gary Brecka?

  30 is normal.

• 1:09:41Speaker 00

  30 doesn't work for me.

• 1:09:43Gary Brecka?

  No, me either.

• 1:09:44Speaker 00

  So 60 to 80, closer to 80, mine's about, mine is about just under 80. And that's where you want it. So that helps keep your microglial cells on your side. That's what you want. So.

• 1:09:57Gary Brecka?

  Yeah.

• 1:09:57Speaker 00

  I've been saying that for a number of years. Let's talk about a couple of interesting studies that just came out. One study that came out this year in the context of a different study, which just floated my boat. I was talking to my best friend, ChatGPT, the other day at, at the gym.

• 1:10:12Gary Brecka?

  Chat's, Chat's a good friend of mine too.

• 1:10:14Speaker 00

  Unpacked this study. I have the best time. I want to hold ChatGPT to the mat on, on going deep on these ideas. So here's what the study, study talked about, that they took a group of people in their 30s and it was several thousand people. They followed them for 16 years. At the beginning of that 16 year prospective analysis, they measured their vitamin D levels. At the 16 year point, they brain scanned them for tau protein. Now, your audience may or may not know what tau protein is all about. I'll back up to study just a minute. JAMA just published a study.

• 1:10:55Speaker 00

  We've known that this phosphorlated tau 217 is a way we can help diagnose Alzheimer's if we're not sure, predicts how quickly a patient will decline. But the new study in JAMA showed that this PTau 217, one of the fundamental blood tests I'd like everyone to get, is predictive of who's going to get it well in advance. Let's get back to the vitamin D study. So the vitamin D levels were looked at in juxtaposition to measuring tau in the brains of people using a special scan. Higher vitamin D, lower tau in the brain.

• 1:11:34Gary Brecka?

  Wow.

• 1:11:35Speaker 00

  Now, to be fair, that's a correlation.

• 1:11:38Gary Brecka?

  Right.

• 1:11:39Speaker 00

  Higher vitamin D, lower tau in the brain. Do I think that's important and therefore supports the idea that we should make sure our vitamin D levels are where they need to be? You bet I think that. Again, that's not what this study allows me to say from a science perspective, but my personal view, which is I guess what all of our views are.

• 1:11:59Gary Brecka?

  Yeah.

• 1:12:00Speaker 00

  Is that you bet you need to maximize or optimize rather your vitamin D level. It's that important. It reduces inflammation. Vitamin D receptors on those microglial cells via make their way to the nucleus and transcribe genes that are doing good things. They make, it makes their way to the mitochondria and helps with energy production. So I'm all in.

• 1:12:22Gary Brecka?

  Okay. So creatine, vitamin D, vitamin D3, anything else that is?

• 1:12:27Speaker 00

  Oh, well, there's lots.

• 1:12:28Gary Brecka?

  Well, that's, we got time.

• 1:12:30Speaker 00

  Third hour. We'll do the third hour.

• 1:12:32Gary Brecka?

  Okay.

• 1:12:33Speaker 00

  And I'll bring this up because an interesting study published about two months ago challenged the wisdom that omega 3 supplements, fish oil in particular, was good for the brain. It was an interesting study that followed, that it looked at records of individuals, whether or not they became demented and cross-referenced that, if you will, with whether they were taking fish oil or not. And concluded that fish oil was of no benefit in reducing risk of Alzheimer's and in fact may have actually slightly increased risk.

• 1:13:05Gary Brecka?

  Oh, wow.

• 1:13:06Speaker 00

  Right. Now, at first blush, a lot of the people watching us right now, your audience, saying, why, that's crazy. I mean, I've known for years that we should be taking DHA, fish oil, omega 3s in general, good for the brain, right?

• 1:13:20Gary Brecka?

  Right.

• 1:13:21Speaker 00

  It's been our messaging and for me, it's still my messaging. Why was this study in the face of all of the studies demonstrating correlations between higher levels of DHA in particular and lower risk of becoming demented, dating back to the original work of Martha Claire Morris from Rush? Why was this new study, in my opinion, off-base and serves as a huge disservice to people? Well, reading the literature or getting informed these days, what's the first thing somebody might reach for if there's developing dementia? Omega 3s.

• 1:14:03Gary Brecka?

  Right.

• 1:14:04Speaker 00

  Right. I mean, what would you tell somebody?

• 1:14:06Gary Brecka?

  Oh, yeah.

• 1:14:07Speaker 00

  My friends who are having, I have a particular friend who's having cognitive decline. What should he or she do? Well, omega 3s should certainly be part of that equation. So you're selecting people out now.

• 1:14:17Gary Brecka?

  Right.

• 1:14:18Speaker 00

  By putting them, these people are going to gravitate to take, demented people or early dementia, subjective cognitive impairment are going to gravitate to the omega 3s anyway. That's going to skew these results. You've already selected a group of people who may be experiencing cognitive decline, number one. Number two, to be fair, there's a lot of crap on the shelves in the grocery store. Being sold as high-quality fish oil in a clear, plastic container that's been sitting there, probably shipped in a hot truck or who knows what? How was it refined? All the things that may not have the efficacy we're looking for, likely it does not.

• 1:14:56Gary Brecka?

  Right.

• 1:14:57Speaker 00

  So for those reasons, and you know, our understanding of the chemistry of DHA, I mentioned one thing that DHA does earlier in our time together today enhances the production of brain-derived neurotrophic factor. DHA is a COX2 inhibitor, i.e. it's an inflammation reducer in the body. Therefore, we need DHA. It's a powerfully important structural component of the neuronal membrane where all the information gets transmitted. It makes up part of the synapse where cells connect to, neurons connect to each other and share information. So don't throw the baby out with the bathwater.

• 1:15:34Gary Brecka?

  I couldn't agree with you more. I take an olive oil in the morning. I take phosphatidylcholine in the afternoons and I also take a fish oil.

• 1:15:41Speaker 00

  So, right.

• 1:15:42Gary Brecka?

  I, yeah, I load up on the.

• 1:15:45Speaker 00

  Yeah.

• 1:15:46Gary Brecka?

  EPA, DHA.

• 1:15:47Speaker 00

  There are plenty of other things that are not, you know, expensive that we should be thinking about, like B complex. A good B complex. Now, might you need a special form of B complex? As I do, because my homocysteine was slightly elevated. Homocysteine, an important lab study, a powerful risk marker for Alzheimer's. You get a homocysteine level now on the various labs that you're able to get bundled without a doctor's prescription. Homocysteine is included. Why? Because it's a powerful risk marker for cardiovascular disease and as such, because it's a risk factor for that, you would expect it to be a risk marker for Alzheimer's and indeed it is.

• 1:16:31Gary Brecka?

  Wow.

• 1:16:32Speaker 00

  But here's the good news. You can drive homocysteine levels down with B complex.

• 1:16:37Gary Brecka?

  B complex and TMG.

• 1:16:39Speaker 00

  Yeah. Trimethlyllicine.

• 1:16:41Gary Brecka?

  Trimethlyllicine.

• 1:16:42Speaker 00

  Or dimethyllicine.

• 1:16:43Gary Brecka?

  Yeah.

• 1:16:44Speaker 00

  Unless you have a genetic quirk, which I have called MTHFR. I don't mean to be too technical, but I will guarantee you, some of your viewers know exactly what I'm talking about.

• 1:16:57Gary Brecka?

  All of my viewers do.

• 1:16:58Speaker 00

  Right.

• 1:16:59Gary Brecka?

  All of my viewers.

• 1:17:00Speaker 00

  MTHFR.

• 1:17:01Gary Brecka?

  I've been standing on MTHFR for 12 years.

• 1:17:02Speaker 00

  Methylcholine tetrahydrofolic reductase.

• 1:17:03Gary Brecka?

  Yes.

• 1:17:04Speaker 00

  And that is a mouthful.

• 1:17:05Gary Brecka?

  Also called the motherfucker gene.

• 1:17:06Speaker 00

  The mofuck.

• 1:17:07Gary Brecka?

  Just say it, Dr. Pomeroy.

• 1:17:08Speaker 00

  Just say it, David. You were going to get me to do that? No, you're going to bleep it out anyway.

• 1:17:12Gary Brecka?

  Okay.

• 1:17:13Speaker 00

  But, so I think that, you know, this is fantastic, fantastic information. Hashtag WTF, why that's fantastic.

• 1:17:23Gary Brecka?

  Yes.

• 1:17:24Speaker 00

  Right? That's what it stands for. That we now have the ability to not only say, well, your homocysteine is elevated, but here's why. So for these MTHFR people, myself included, we know that we are at risk for elevated homocysteine and other issues by virtue of the fact that we don't methylate. And we can fix that by taking not just B complex vitamins, but they have to be methylated. Methylfolate, methyl B12, problem solved. My, my homocysteine went down to 6.8.

• 1:17:55Gary Brecka?

  Same with mine. Mine was 15, now it's seven.

• 1:17:57Speaker 00

  So if you had a homocysteine of 15, that needed work. And who knows how long in your life, you didn't know this.

• 1:18:05Gary Brecka?

  My whole life, well, six, eight years ago.

• 1:18:09Speaker 00

  Yeah.

• 1:18:10Gary Brecka?

  Yeah. I've supplemented ever since.

• 1:18:12Speaker 00

  And there are people that we will talk about perhaps off-camera for whom we need to know their homocysteine levels and vitamin D levels and all the things right now. I mean, we talked about the microbiome and all that, all well and good. These other things are very powerful levers.

• 1:18:26Gary Brecka?

  Yeah.

• 1:18:27Speaker 00

  And will allow us to really make headway.

• 1:18:28Gary Brecka?

  First of all, I agree with everything you're saying. The methylated multivitamins, the methylfolate, methylcobalamin version of B12, some genetic variants need the hydroxy or the adenosyl.

• 1:18:41Speaker 00

  And it's not a big deal, Sam.

• 1:18:43Gary Brecka?

  It's super easy.

• 1:18:44Speaker 00

  It, you know, I look forward to my sublingual B12 because it's sweet and it's the only, you know, it's my real treat, my sublingual B12. Sometimes I might even have two if I'm feeling like I reward myself.

• 1:18:56Gary Brecka?

  Yeah.

• 1:18:57Speaker 00

  That's how lame I am.

• 1:18:58Gary Brecka?

  Eat little, so little sugar, you mean?

• 1:18:59Speaker 00

  Oh, yeah, but I will have dark chocolate.

• 1:19:01Gary Brecka?

  Yeah.

• 1:19:02Speaker 00

  You know, I have 85% and that has very little sugar. And fruit I eat and it's got, it's got sugar and I'm well aware of that, but you know.

• 1:19:08Gary Brecka?

  Yeah, fruit, honey and maple syrup are where I get my sweets from.

• 1:19:11Speaker 00

  And then I use allulose.

• 1:19:12Gary Brecka?

  Allulose is.

• 1:19:13Speaker 00

  You've covered.

• 1:19:14Gary Brecka?

  Magic.

• 1:19:15Speaker 00

  Yeah. It's magic and until it isn't, but I think it's, it's, for me, it's.

• 1:19:20Gary Brecka?

  I would agree with you.

• 1:19:21Speaker 00

  A very important player.

• 1:19:22Gary Brecka?

  As a, call it artificial sweetener. It's not actually an artificial sweetener.

• 1:19:26Speaker 00

  It's actually natural.

• 1:19:27Gary Brecka?

  But, no, I don't want to call it an artificial sweetener.

• 1:19:29Speaker 00

  But it is, it is manufactured.

• 1:19:31Gary Brecka?

  Alternative, whatever you want.

• 1:19:32Speaker 00

  And.

• 1:19:33Gary Brecka?

  Because I don't want to throw it in there with aspartame and all that other nonsense.

• 1:19:36Speaker 00

  No. And, you know, I think that perhaps monk fruit's innocuous. I, you know, I'm not a fan of the aftertaste of stevia.

• 1:19:45Gary Brecka?

  They cut it a lot with erythritol, but the pure monk fruit.

• 1:19:48Speaker 00

  Yeah, and I think the data relating higher levels of erythritol consumption to cardiovascular risk is real. I, you know, they're.

• 1:19:57Gary Brecka?

  I read that.

• 1:19:58Speaker 00

  Yeah. And so, but you know, if you're chewing erythritol sweetened gum, I can't think you're getting a huge dosage of erythritol.

• 1:20:04Gary Brecka?

  Right.

• 1:20:05Speaker 00

  But if this is compared to sugar, then you've made the right choice.

• 1:20:10Gary Brecka?

  Right.

• 1:20:11Speaker 00

  So, oh, but it's natural. It's cane sugar. It's coconut sugar. It, call it what you will, it's sugar. It's sugar. And, oh, but it's organic and somebody, you know, put crystals over it, whatever. I don't care. It's sugar. You gotta stop.

• 1:20:28Gary Brecka?

  Right.

• 1:20:29Speaker 00

  And gosh, this Dr. Pomeroy is a pain in the ass, isn't he?

• 1:20:31Gary Brecka?

  Yeah.

• 1:20:32Speaker 00

  I mean, he's making, and the reason I am this pain in the ass is so that when you're my age, you'll be able to have hopefully what sounds like an intelligent conversation about intriguing topics and you'll be able to satisfy your curiosity, remain curious, remain engaged. You're doing your best to keep your physical body.

• 1:20:51Gary Brecka?

  And remain independent.

• 1:20:52Speaker 00

  You know, that's.

• 1:20:53Gary Brecka?

  And remain what?

• 1:20:54Speaker 00

  Independent.

• 1:20:55Gary Brecka?

  Independent.

• 1:20:56Speaker 00

  That's the thing that I, you know, my heart bleeds so much for my parents is their losing independence.

• 1:21:01Gary Brecka?

  Losing agency.

• 1:21:02Speaker 00

  Yeah. And losing agency and, you know, and, and that to me is, you know, the definition of, of your life's decline. I mean, most of us, I think, if we had the choice of lifespan or health span, would say, I want the longest lifespan with the longest health span. But as my health span starts to go off a cliff, you know, there's not a whole lot of joy to drive out of life.

• 1:21:27Gary Brecka?

  Yeah. And you know, the worst situation is people who remain kind of physically.

• 1:21:32Speaker 00

  In fairly good, good stead, but cognitively decline.

• 1:21:36Gary Brecka?

  Yeah.

• 1:21:37Speaker 00

  It's just tragic.

• 1:21:40Gary Brecka?

  Yeah. So I, first of all, I agree with and love everything you've said so far.

• 1:21:44Speaker 00

  Uh oh.

• 1:21:44Gary Brecka?

  Yeah, I do. I mean, I'm in the

• 1:21:46Speaker 00

  So I got a good score going into the final here.

• 1:21:48Gary Brecka?

  I mean,

• 1:21:49Speaker 00

  Double point questions are coming soon.

• 1:21:51Gary Brecka?

  Great score.

• 1:21:53Gary Brecka?

  So any, any other supplements, and then I want to shift to some modalities. I actually want to get your opinion right out in the open on, on some of the things I'm doing for my mom, which include

• 1:22:05Gary Brecka?

  transcranial red light, uh, which is saturating her brain with red light, certain wavelengths of red light known to be therapeutic, specifically the ones that dissociate mitochondrial nitric oxide from cytochrome c oxidase to

• 1:22:21Gary Brecka?

  force oxygen, for lack of better words, into the mitochondria to change this metabolic cycle of the

• 1:22:26Speaker 00

  I, I wrote about them.

• 1:22:27Gary Brecka?

  You did?

• 1:22:28Speaker 00

  Oh, it's red lights and, and

• 1:22:29Gary Brecka?

  Okay, great.

• 1:22:30Speaker 00

  And, uh, but you know, uh, it may seem hokey. It isn't. Uh, we are, you know, we, we see what it's doing in laboratory animals. That it is able to penetrate into the brain, that it is powerfully effective in terms of what you just mentioned and reducing inflammation, which from a microglial perspective is a home run.

• 1:22:50Gary Brecka?

  Right.

• 1:22:51Speaker 00

  And, uh, enhancing

• 1:22:52Gary Brecka?

  And directly targeting the mitochondria. It's, it's hard

• 1:22:56Speaker 00

  Mitochondrial therapy.

• 1:22:57Gary Brecka?

  Target them, right? Um, you know, to just

• 1:23:01Gary Brecka?

  select the mitochondria, because there, there's a a long distance between, let's say oral supplementation and getting through the mitochondria and getting into one of those stages of the Krebs cycle electron transport chain. And, and light, uh, can do that. I mean, it ignores the cell wall, ignores the mitochondrial membrane and goes into certain complexes and, and actually exerts a measurable effect.

• 1:23:26Speaker 00

  Well, that's what the, uh, the beauty of, one of the things I mentioned earlier, this RNS60 mo- uh, instantly just transgresses, makes its way into the mitochondria.

• 1:23:35Gary Brecka?

  What was the RNS?

• 1:23:36Speaker 00

  So RNS60 is a, a, uh, nano particle change of saline, normal saline, make a hyperoxygenating normal saline. Clinical trials so far in ALS, extending life by six months, but dramatically preserving respiratory function and speech, pretty, uh, pretty significant, I'd say. And cutting a hospitalization time in half, uh, in individuals who've experienced a stroke.

• 1:24:07Gary Brecka?

  Wow.

• 1:24:08Speaker 00

  Yeah.

• 1:24:09Gary Brecka?

  And where do you get this?

• 1:24:11Speaker 00

  Well, this is experimental.

• 1:24:13Gary Brecka?

  Oh, it's going through trial.

• 1:24:14Speaker 00

  No, well, it's being used for developed for scientific research. Though that may change.

• 1:24:20Gary Brecka?

  Can you?

• 1:24:20Speaker 00

  One would hope.

• 1:24:21Gary Brecka?

  Can you get ahold of it now?

• 1:24:23Speaker 00

  No.

• 1:24:23Gary Brecka?

  No.

• 1:24:24Speaker 00

  It, I

• 1:24:25Gary Brecka?

  You have it though.

• 1:24:29Speaker 00

  Oh my God.

• 1:24:31Gary Brecka?

  Busted.

• 1:24:32Speaker 00

  Busted.

• 1:24:33Gary Brecka?

  All right, we'll talk after the podcast.

• 1:24:35Speaker 00

  But, uh, having said that, um, the company is called Revelatio, Revelatio.

• 1:24:41Gary Brecka?

  Revelatio.

• 1:24:41Speaker 00

  And their, uh, their science is just so forward thinking. Yeah, very, very exciting. And you know,

• 1:24:49Gary Brecka?

  Oxygenating saline. So, um, just trying to think of the mechanism there. Interesting.

• 1:24:55Speaker 00

  Yeah. Um, but, but I mean, there are protocols now, uh, being done, uh, in humans to transplant healthy mitochondria into humans. The first studies were in, uh, children who have had, uh, required heart surgery and couldn't come off what's called the ECMO pump, the oxygenation pump afterwards. By transplanting mitochondria uh, into their hearts have had a dramatic, uh, increased ability to come off of ECMO and survive.

• 1:25:24Gary Brecka?

  Where do they get the mitochondria?

• 1:25:26Speaker 00

  Well, they're, uh, developed, they're taken from the leg muscle, actually.

• 1:25:30Gary Brecka?

  So you relocate mitochondria from functional areas of the body?

• 1:25:33Speaker 00

  Right, spin them down and then

• 1:25:34Gary Brecka?

  Hypofunctional areas.

• 1:25:35Speaker 00

  Can you imagine?

• 1:25:36Gary Brecka?

  That's

• 1:25:36Speaker 00

  The idea of transplanting mitochondria into the brain? I mean, it, you know, we're, we're scratching our heads right now thinking, oh my gosh, could that ever happen? Look what's happening right now.

• 1:25:46Gary Brecka?

  Right through the cribriform plate or some kind of intranasal?

• 1:25:48Speaker 00

  The cribriform perhaps, uh, but I would think first it'll be injected, uh, into the ventricles, uh, into the spinal fluid itself. But, um, uh, there are, uh, but, but using the cribriform for this monoclonal antibody, this ferral, ferralumab, uh, that's being developed at Brigham and Williams, uh, Brigham and William.

• 1:26:08Gary Brecka?

  It's small enough to pass through?

• 1:26:10Speaker 00

  Oh, it's a monoclonal antibody, makes its way right through. Yeah. Uh, there's a lot of things being delivered, uh, via this nasal, even, um, exosomes now. But that said, uh, even microglia, healthy microglia are being created from, uh, stem cells, uh, and through CRISPR intervention become microglia. The M2 supportive microglia and already a human trial has been, uh, undertaken for not, it's, it's a different ALS, not the one you're familiar with, called ALSD, which is almost uniformly a fatal condition. And basically has arrested the disease, uh, by giving them healthy, good functioning mitochondria. It is a,

• 1:26:52Speaker 00

  it has been defined as a defect of mito- of, uh, microglial function by giving them healthy microglia. Let me make sure, I think I said mitochondria.

• 1:27:01Gary Brecka?

  Yeah, mitochondria.

• 1:27:02Speaker 00

  By giving them healthy microglial cells into their brains, basically saving these people's lives.

• 1:27:09Gary Brecka?

  Wow.

• 1:27:09Speaker 00

  Pretty astounding.

• 1:27:10Gary Brecka?

  And again, where are they getting the microglial cells? So they

• 1:27:13Speaker 00

  These are created from, from stem cells, basically.

• 1:27:16Gary Brecka?

  Wow, that is so fascinating. I'm a big fan of exosomes, um, especially because of their particle size, about a one eight hundredth the size of

• 1:27:24Speaker 00

  Yeah, and recently a study was published where exosomes were created from human cells that were, were like microglial cells, but just a little bit, uh, earlier in their development. From these human cells, exosomes created, administered intranasally to the laboratory mouse model of Alzheimer's disease and having really a profound effect on reducing beta amyloid load. We talked about why that may or may not be critical.

• 1:27:53Gary Brecka?

  Right.

• 1:27:54Speaker 00

  But also improving their cognitive function, preserving their cognitive function by giving them intranasal exosomes derived from human microglia, like human, like microglial cells.

• 1:28:06Gary Brecka?

  So your, your position clearly is Alzheimer's is something that is highly preventable. Given the right lifestyle factors, um, and may have some very, very promising treatment alternatives to what's out there right now.

• 1:28:23Speaker 00

  Yeah, and that's right. And I, I look at what the near horizon looks like and the far horizon for that matter, in terms of what people are looking at, uh, through the lens of these microglial cells to bring about improvement, bring about, I would hope for a cure of this situation. And again, it's not just that your guest today is saying that lifestyle issues, uh, can reduce the risk of this happening. This was published in the journal, The Lancet in 2024. Their, the Lancet commission indicated that if we could pay attention to 14 modifiable factors, that the incidence of, uh, dementia could be reduced by as much as 50%.

• 1:29:06Gary Brecka?

  Wow.

• 1:29:07Speaker 00

  It was an interesting

• 1:29:08Gary Brecka?

  I assume that is applicable to Alzheimer's too. I mean,

• 1:29:11Speaker 00

  Oh yeah, Alzheimer's is the most common cause of dementia by far and away. Uh, it was interesting though, and I've said this before, and I, uh, that they didn't mention diet. So I wrote, I, along with the guy, Dr. Robert Lustig, where, uh, we wrote this letter to the editor to the Lancet and said, hey, here are the multiple studies talking about the various diets, uh, whether it's Mediterranean, Mediterranean plus, the mind diet, you name it. And how they play out in terms of dementia risk. So we, we're sure this was just an oversight and, uh, and we got a pat on the back and said, we're not going to publish your letter to the editor.

• 1:29:48Gary Brecka?

  Ah, wow. Okay. Well, there's a lot of, uh,

• 1:29:53Speaker 00

  Why, you know,

• 1:29:54Gary Brecka?

  Forced to be out there.

• 1:29:56Speaker 00

  Yeah.

• 1:29:56Gary Brecka?

  Yeah. Don't want us to think that food is medicine.

• 1:30:00Speaker 00

  Yes, and, and let me say that

• 1:30:01Gary Brecka?

  Exercise is medicine.

• 1:30:02Speaker 00

  We've talked about the broad strokes. I'm happy if that's the only message that lands, because it's huge. Uh, exercise, diet, sleep.

• 1:30:11Gary Brecka?

  Being in the presence of other people.

• 1:30:14Speaker 00

  Yeah.

• 1:30:15Gary Brecka?

  Not often talked about as a huge issue, but when you go back to the blue zones, those who were, who lived the longest.

• 1:30:20Speaker 00

  Isolation.

• 1:30:21Gary Brecka?

  And the healthiest, isolation is a major risk for developing Alzheimer's disease. Don't be isolated. And if your elders are isolated, do what you can to make that not happen anymore.

• 1:30:34Speaker 00

  I could not agree with you more.

• 1:30:36Gary Brecka?

  Even if it's virtual, even if they have a pet.

• 1:30:41Gary Brecka?

  Looking into the eyes of a dog has powerful effects on your microglial cells.

• 1:30:46Speaker 00

  Wow.

• 1:30:47Gary Brecka?

  Think about that. That's why I was greeted when I walked in here by your dog.

• 1:30:51Speaker 00

  Yeah.

• 1:30:51Gary Brecka?

  And I felt, God, you're catering to my microglial cells.

• 1:30:54Speaker 00

  I got hosed in that one. I lost that battle. My youngest daughter convinced me that we were sheltering, like we were fostering. That was the term she used. We got it from the shelter. She, we were going to foster it for like two weeks and then.

• 1:31:10Gary Brecka?

  It never works.

• 1:31:10Speaker 00

  It's going to go to another home.

• 1:31:11Gary Brecka?

  That never works at all.

• 1:31:12Speaker 00

  That's been what, six, seven months now, eight months.

• 1:31:15Gary Brecka?

  No, I'm glad to see that you have a dog.

• 1:31:17Speaker 00

  It's, that's great. He's, he's, he's here now permanently.

• 1:31:21Gary Brecka?

  You know, we've seen that data.

• 1:31:22Speaker 00

  He's a great dog. Looks like a pit bull, so he looks very scary, but he's just a giant teddy bear.

• 1:31:27Gary Brecka?

  He jumped up on me. I thought it was great. Licked me. Um.

• 1:31:30Speaker 00

  Yeah.

• 1:31:31Gary Brecka?

  That's all, that's all good.

• 1:31:32Speaker 00

  He's a teddy bear.

• 1:31:32Gary Brecka?

  You know, how does it work? Well, we could talk about lack of social engagement, isolation, amps up cortisol. Cortisol is immediately and directly threatening to the health and mitochondrial function, I might add, in the hippocampus, the brain's memory center itself.

• 1:31:51Speaker 00

  Fascinating. When we were in the, this is going back years, but in the mortality space,

• 1:31:58Speaker 00

  we knew that isolation had a dramatic, there's a lot of data around this, by the way.

• 1:32:05Gary Brecka?

  Oh, yeah.

• 1:32:06Speaker 00

  A dramatic effect on lifespan. I mean, we know about broken heart syndrome, right? I mean, you show me a couple, married 40, 50, 60 years, one passes away. The other one usually goes very quickly. And when we had these second to die policies or permanent universal life policies, we had a lot of data on isolation. And it accelerated all cause mortality. And you know what else? Anecdotally, when you think some of the most horrific crimes, you know, when you read the paper and you're like, who's that committed by? Oh, that was a kid that never talked to anybody. He was the most isolated, never came out of his room.

• 1:32:41Gary Brecka?

  He always kept a clean room. Have you ever noticed that?

• 1:32:46Speaker 00

  Yeah.

• 1:32:46Gary Brecka?

  So.

• 1:32:47Speaker 00

  They interview somebody, you know?

• 1:32:48Gary Brecka?

  Yeah. So the isolation is a major factor. And you're right, the blue zones, community, connection, prayer.

• 1:32:58Speaker 00

  Yeah. I mean, that's what Dan Buettner called out. It's not a pill. It's not a specific dietary recommendation. Yes, these people felt engaged in their communities. And it's huge. The.

• 1:33:11Gary Brecka?

  They felt, they also felt a purpose, you know, like.

• 1:33:13Speaker 00

  Exactly.

• 1:33:14Gary Brecka?

  Why am I here? You know, when, when an elderly person is just sitting around alone all day, for days on end, you know, I, my grandmother's sister was like this.

• 1:33:30Gary Brecka?

  You know, they're just alone with their, in their own thoughts. And you know, they gotta think.

• 1:33:33Speaker 00

  It's hugely destructive.

• 1:33:34Gary Brecka?

  Why am I here?

• 1:33:35Speaker 00

  We could talk about mechanistically what may be going on. Well, we know that that's a stressful situation. Cortisol levels go up, as I mentioned a moment ago, threatening directly to the hippocampus. Dr. Robert Sapolsky talked about that 25 years ago. In primates who constantly were under threat, looked at their hippocampus after postmortem and they were shrunken.

• 1:33:55Gary Brecka?

  Yeah, that's memory.

• 1:33:56Speaker 00

  But, but beyond that, what's the upside here of engagement? What happens when you're with people, looking them eye to eye as you are right now? My oxytocin level, my love hormone is going up.

• 1:34:08Gary Brecka?

  Right.

• 1:34:09Speaker 00

  And oxytocin is bound to the supportive microglial cell and tells them.

• 1:34:15Gary Brecka?

  Wow.

• 1:34:16Speaker 00

  You better just stay in this M2 configuration and be a brain defender. So you're, you right now are keeping my microglial cells, along with your dog, am I right? In their supportive role because we are in a situation where we're feeling good about each other. We're having feelings of love and because we're doing good things. And so, you know, if you have to break it down to mechanism, okay, there are some mechanisms, but we just inherently know that to be true.

• 1:34:43Gary Brecka?

  Yeah.

• 1:34:43Speaker 00

  If, if you ever watch Alone, you watch a TV show Alone? I've seen times when, my gosh, there's a contestant and it's who can last the longest on their own. I mean, these people build musical instruments, a canoe, a house, you know, a hot tub, all these things they're building. This guy's going to win. Home run. He's great, you know, and the next, you know, he says, look at all this stuff I've built. I can't take it anymore.

• 1:35:12Gary Brecka?

  Yeah.

• 1:35:13Speaker 00

  He pushes, he calls them the next and they pick them up.

• 1:35:15Gary Brecka?

  Yeah.

• 1:35:16Speaker 00

  Because it's just very, very stressful to be alone.

• 1:35:19Gary Brecka?

  Yeah.

• 1:35:20Speaker 00

  And again, it can be virtual, but we've got to keep people in the loop.

• 1:35:25Gary Brecka?

  Yeah, love it. Dr. Perlmutter, this is amazing. My VIPs are, are waiting with a whole list of questions for you. Cause I.

• 1:35:35Speaker 00

  They're holistic.

• 1:35:36Gary Brecka?

  Told them that you were coming on the podcast, so we're gonna, we're gonna head over there to the VIP group. But before we do, I end all my podcasts by asking my guests the same question. And that is, and this can be an interesting answer coming from you. What does it mean to you to be an ultimate human?

• 1:35:52Speaker 00

  To be an ultimate human means to identify your skill set and exploit it to its fullest.

• 1:36:00Gary Brecka?

  Wow. That's probably another way of saying fulfill your purpose.

• 1:36:04Speaker 00

  Exactly.

• 1:36:04Gary Brecka?

  Right? Skill set.

• 1:36:05Speaker 00

  Identify it and fulfill it.

• 1:36:07Gary Brecka?

  Identify and fulfill it. That is one of the most succinct answers I think we've ever gone.

• 1:36:11Speaker 00

  Well, I think that everybody has something.

• 1:36:13Gary Brecka?

  Yeah. Well, this has been a great pleasure for me. Really, 2014 was a game changer for me when I read your book. It really had a long lasting impactful, impact on my career and was part of.

• 1:36:29Speaker 00

  I'm very, very honored and happy to hear that.

• 1:36:32Gary Brecka?

  Yeah.

• 1:36:32Speaker 00

  Thank you.

• 1:36:32Gary Brecka?

  Really did. And I'm looking forward to reading this book because it also is very appropriate for the position that I'm in with, with my loved ones. And I'm going to share that on the, on my platform. But thank you so much for coming on the Ultimate Human Podcast today.

• 1:36:47Speaker 00

  Lots more work to do.

• 1:36:48Gary Brecka?

  Yeah, no, no, I'm gonna, I'm gonna have you back. I mean, especially as I get through this book, I'm gonna have a whole nother podcast full of questions.

• 1:36:55Speaker 00

  Yeah, sure.

• 1:36:55Gary Brecka?

  And until next time, guys, that's just science.