# Dr. David Perlmutter on Menopause, Metabolism & Protecting Your Brain

An episode of [Live Like a Girl with Dr. Mindy Pelz](https://invisiblenetwork.ai/podcast/1503897906), 24 Aug 2026, 1 h 06 min.

Audio: https://media.transistor.fm/79db1925/632dfefa.mp3

Women are far more likely than men to develop Alzheimer’s disease, and Dr. David Perlmutter believes one of the most important pieces of that story is metabolic health. In this episode of Live Like a Girl, Dr. Perlmutter joins Dr. Mindy to explain what happens when the brain’s immune cells shift from protective to destructive, why menopause may increase vulnerability, and how blood sugar, insulin resistance, visceral fat, inflammation, mitochondrial health, and lifestyle all influence brain aging. They also discuss HRT, GLP-1 medications, ketones, fasting, fiber, exercise, BNDF, sleep, and what women can begin doing in their 30s, 40s, and 50s to support long-term cognitive health. In This Episode, You’ll Learn • Why women face a higher risk of Alzheimer’s • How menopause may affect brain metabolism • Why belly fat and insulin resistance matter for brain health • The blood markers Dr. Perlmutter watches most closely • What emerging research says about GLP-1 drugs and the brain • The lifestyle habits Dr. Perlmutter prioritizes for prevention Resources Mentioned • Brain Defenders • Tanzi Study • Cochrane Review More on Dr. David Perlmutter • https://drperlmutter.com/ • http://braindefenders.com/ • https://www.instagram.com/davidperlmutter/ • https://www.youtube.com/user/DavidPerlmutterMD • https://x.com/davidperlmutter • linkedin.com/in/david-perlmutter-md For more resources related to today’s episode, visit the podcast episode page: https://www.drmindypelz.com/ep363/ Connect with Dr. Mindy: • Join Reset Academy • Watch the episodes on YouTube • Follow Dr. Mindy on Instagram • Subscribe to Dr. Mindy’s newsletter Disclaimer: This podcast is intended for educational and informational purposes only and is not a substitute for professional medical advice. Always consult a qualified healthcare professional before making changes to your diet, fasting routine, or lifestyle.

## Transcript

\[00:00:00:00 - 00:00:23:16\]
(Gentle Music) Hey, Dr. Mindy here, and welcome to the Live Like a Girl podcast, where I bring you icons, disruptors, educators, scientists, and doctors that show you what can be possible when you love and celebrate the female body you are blessed to live in. Let's dive in.
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Two out of every three people diagnosed with Alzheimer's are women. That is twice the risk for men. This is a statistic that as a society, we should be incredibly concerned about. Why women? What is happening to a woman that sets us up for cognitive decline?
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Recently, a large piece of this Alzheimer's conversation for women has centered around the loss of estrogen. Get on hormone replacement therapy and your chances of Alzheimer's diminishes. Today's guest has been studying the brain for decades and has a whole lot more to say about why women are more prone to Alzheimer's than men. And it's not centered around hormone replacement therapy. He actually brings to the table an explanation as to why the belly fat that appears during your menopausal years might be the greatest predictor of cognitive decline.
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Now, hear me out for a moment because this conversation is not there to set you up for shame.
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It's here to help you widen your lens as to the importance of why metabolic flexibility may not only help you lose weight, but sets you up for better brain aging. For years, the belly fat, so many women fight in perimenopause has been treated like a vanity problem, something to shrink for the mirror, for the genes, for how we feel at the beach. But what if the belly fat is actually a warning light for your brain?
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Here's what I learned. The fat gathering around your waist during perimenopause doesn't just sit there. It's metabolically active. And it's pumping out inflammatory signals that travel straight to your brain. Once there, they can flip your brain's own immune cells from protectors of your brain cells into destroyers, cells that start dismantling the very connections they're supposed to defend. And in women, that flip gets an extra push from falling estradiol, which starts to send its own signal telling those cells to start tearing things down. It is, in every functional sense, your body turning on itself, a bit like an autoimmune condition for the brain. So that waistline that you're concerned about, I promise you, it is more than just cosmetic. It's a metabolic marker. And it may be one of the most powerful predictors we have for Alzheimer's risk, more useful than any brain scan. So this is why I have brought you Dr. David Perlmutter. Dr. Perlmutter is a board certified neurologist and author of the New York Times best-selling book, Grain Brain, which I highly recommend. His new book, Brain Defenders, lays out exactly how these brain immune cells decide whether to protect you or turn against you and how the same lifestyle that works on shrinking your waistline can protect your mind. In this conversation, we get into why your waist to hip ratio might tell you more than any test in a neurologist's office and why prevention, not a future cure, is where your real power lies. I love this conversation. I hope you are inspired by what you hear. I hope it motivates you to go into not just wanting to become more metabolically flexible so you feel good and you look good, but so you can finally prevent cognitive decline.
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So without further ado, let's dive in. Dr. David Perlmutter.
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Dr. Perlmutter, let me just start off by saying welcome to my podcast. I'm really excited to have this conversation. And for your viewers and listeners, we've already had a really nice conversation so I know we're gonna have a great time today. Yeah, here's what I'm really curious about. A third of Alzheimer's happens to women, yet in all the research I've seen,
\[00:05:20:11 - 00:06:25:18\]
there is no real solution for these women and yet perhaps the solution isn't in medication, the solution is in lifestyle. Help us understand the difference when we're treating a brain condition like Alzheimer's between taking a medication and actually putting the work in your lifestyle. The most important things to consider about what is going on in the Alzheimer's brain is it is a manifestation of a shift in the brain's immune cells away from being supportive, what we call brain defender cells, to being destructive. These exact cells can either be on your side and helping your brain remain healthy or they can shift and turn their backs on you and lead to the destruction of synapses. To be fair, that process happens in men and women. It's the exact same process but we have to go a little bit upstream and unpack a term called immunomatabolism. These are immune cells, that's the immuno part, the brain's immune cells called microglial cells.
\[00:06:26:22 - 00:09:42:23\]
But let's talk about metabolism. So this is when we begin to find some areas of explanation in terms of why women are twice as likely to develop Alzheimer's in relationship in relation to men in comparison to men. Yeah, there are hormonal issues and we're going to unpack those, that's for sure. But I think fundamentally for both genders, we've got to understand that upstream of this accumulation of beta-emiloid that seems to get all the attention, which is not warranted, are the fundamental issues related to changes in the metabolism of the brain that plays out as changes in the brain's immune system becoming threatening. That's the fundamental that underpins our entire time together today. So women are at higher risk. We know that these immune cells seem to be more primed when suddenly in women, estradiol levels fall. And that happens in perimenopausal time, that hormone changes are pretty dramatic. Estradiol E2, a type of estrogen, it falls precipitously as it does during menopause, somehow labels the synapses, one brain cell connected to the next brain cell. And that is a signal for these brain immune cells to destroy the synapses. That's pretty powerful. Fascinating, like an autoimmune condition? It is, you know, it's not a classic autoimmune condition, but is it an autoimmunity 100%? It's the body's immune system turning on itself. It's exactly what's going on. It's not lupus, it's not rheumatoid arthritis, the classic celiac disease, type 1 diabetes that we discuss, but you hit the nail on the head. It is absolutely an immune issue of the human body, but importantly here, now we know why. It's because fundamentally the metabolism of those immune cells has changed, and that's what causes them to change from being friend to being foe. What is so important, again, for our time together today, this is one of the bullet points if you had bullet points, is that the metabolism of these brain immune cells that determines whether you're going to have a brain that's
\[00:09:44:02 - 00:12:05:18\]
to the idea of preventing Alzheimer's in the first place, heaping our metabolism on track. I mean, to be fair, the most powerful risk factor for the development of Alzheimer's happens to be our chronological age. We know that women live longer than men, and therefore that's at least a partial explanation as to why they are at greater risk. But menopause in and of itself is associated with obviously these dramatic hormonal changes, but also very dramatic metabolic changes in the brain, and through what I'm now describing, the relationship between metabolism and immunity, called immunomatabolism, it affects these brain immune cells to virtually again become our brain destroyers and gobble up the synapses and leads to loss of connectivity. That's what defines these neurodegenerative diseases, is loss of connectivity of one brain cell to the next. So the networks just decline. We know that women in the perimenopausal period have a greater risk of issues with their glucose metabolism. Right, yep. That affects the brain and ultimately challenges their synapses, so there's a lot going on. All of this kind of converges more so in the woman's brain in comparison to the man's brain, in producing excessive inflammation. And that is a powerful activator of these brain immune cells. So would it be fair to say that the woman who's going through perimenopause and all of a sudden got all this belly fat, that there tends to be, and I mean this with complete compassion, frustration around the vanity aspect of that extra weight around the belly, but is that extra weight a sign that the brain is going to follow because there's a metabolic disruption happening through this hormonal change? Mindy, when I'm asked, well what is the, what are the best tests? Here's my response. One of the best things you can do to determine your risk for Alzheimer's is to go out and buy a very, very expensive, highly technical instrument called a measuring tape.
\[00:12:06:20 - 00:15:53:17\]
You put that measuring tape around your belly and you put it around your hips. And you determine based on those measurements the waist to hip ratio. And when that number elevates, that is a powerful risk factor for the development of Alzheimer's disease. That's a metabolic issue. That's one of the five cardinal findings, elevated waist hip ratio of metabolic syndrome. And it works the same in men. So you are exactly right. Why so? Because when we have a higher waist hip ratio, our bellies are getting bigger, that is pro-inflammatory and is also associated with elevated blood glucose and reduction in how insulin works in the human body. And dare I say, in the brain, we should put that on the bulletin board here because we'll get back to that. But the idea that this increase in belly fat is pro-inflammatory is so fundamental. Why? Because the chemicals of inflammation that are called inflammatory cytokines that are produced by this excessive belly fat make their way to the brain. And in the brain, these microglial brain immune cells see those inflammatory cytokines and that causes them to shift immediately from being brain defenders to being brain destroyers. It's that straightforward. So interesting. Yeah, it's why to be more sophisticated, yes, we can measure markers of inflammation like C-reactive protein that correlates with Alzheimer's risk. We can certainly look at blood glucose measurements and correlate that with Alzheimer's risk and even hemoglobin A1C and fasting insulin for that matter. We know that type two diabetics may have as much as a three-fold increased risk for Alzheimer's, a disease for which there is no meaningful pharmaceutical treatment. And I say it like that because it's so important we challenge the current paradigm of live your life however you want, be sedentary, eat whatever crap you want, cause you like it and then know or think you know that there's an Alzheimer's medication that's gonna help you. That is not where we are as we have this
\[00:15:54:23 - 00:17:49:23\]
Okay, here's what I propose we do. Let's prevent the disease in the first place. Then we won't be in this predicament. We were not paying ourselves into a corner. Right. But there's nothing heroic about preventing a disease. You don't get the glory and it's-- No, you don't know you prevented it. Right. I always think you don't even know the disease you would have gotten. But it's the right thing to do. It's a hard thing to do. I know, it's an interesting moment. And it's not remunerative. Nobody's making money off of it. Of you not getting sick. Keeping people healthy, who knew? Okay, it's better to light the candle than curse the darkness, I get that. And therefore you and I have this conversation today. For anyone who's listening, who wants to learn what's going on and to really begin a program for protecting their brains, becoming the architect of their brain's destiny, then you and I are all in. Yeah, you know what's interesting is that in the menopause space right now, the message that women are getting is that your brain, your symptoms, they are occurring because you didn't get access to hormone replacement therapy. We read that study wrong. And one of the things I've done in all my research and in everything I've seen with women is you change their metabolic health and you change all of those menopausal symptoms. So where does HRT fit into this equation? Is this as simple as put a patch on and you're not gonna get Alzheimer's? Let me, I will answer that question. Let me go back to the part about the metabolic issues. So we know that women are certainly at higher risk for cardio metabolic issues. And I don't, what about that term? Cardio metabolic. Why not neuro metabolic? Why not osteometabolic? Well said.
\[00:17:51:07 - 00:20:00:14\]
So everything's affected by its metabolism. Why did, how did the heart end up getting all the glory here? But the issue is that these metabolic changes that are more common in women affect the metabolism of the microglial cells and shifts them to being destructive as opposed to being supportive. You know, the number one cause of death in America in women is cardiovascular disease because they are cardio metabolically compromised. And your point is well taken. And the idea that you would say to your audience, not just today, but in multiple times on your podcast and in your outreach, that when we get the metabolism right, hormones fall into place. Who knew, right? Who knew? And it's so forward thinking and it's so dialed in because when metabolism has gone awry, blood sugars elevated, waist hip ratio changes, blood lipids are compromised, blood pressure is elevated. It increases inflammation and inflammation threatens the functionality of the hormones and their production as well. Their production is dependent on good metabolism, good mitochondrial function, which declines in women as they become metabolically compromised by definition. So is it as simple as putting on a hormone replacement patch? No, it is not. So the idea, and I came out in Brain Defenders as being supportive, by the way, of HRT. But I think timing is really important. We can talk about that in a minute. But could that be effective? I think it's a very important piece of the puzzle. As you well know, Dr. Lisa Moscone right now had engaged a trial, a blinded trial, to determine what is the risk reduction of dementia in women who do receive appropriate, when I say appropriate, I mean not conjugated estrogens, et cetera, but appropriate hormone replacement therapy with natural progesterone, et cetera. What is their risk reduction? Is there a risk reduction in comparison to those who do not or receive placebo?
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That's going to be a big study. I think I know the results. But again, timing is really important. But getting back to the fundamental of your question,
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it's a piece of the puzzle. When we improve metabolism by paying attention to lifestyle choices, then by default hormones are going to improve. Sensitivity of those hormones, their receptor will improve. And I'm not going to say problem solved, but this goes a long way. And it's so important to recognize that these metabolic issues that ultimately play out as reduction in cognitive function and other neurodegenerative issues, the metabolic issues begin in our 30s and 40s. It's not like wait till you're cognitively impaired that we should begin thinking about what to do for you. Oh, we'll give you this IV therapy that doesn't work. It's time to really think about the idea of prevention and keeping the brain healthy through the continuum. The seeds for Alzheimer's are sown in our 30s and 40s in the form of the metabolic issues that are becoming pretty evident at that point.
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It's interesting. I always tell my audience that when you hit 40, the one number you should look at, the one piece of your blood work is hemoglobin A1C. If you can get hemoglobin A1C as close to five as possible, that will tell you your menopausal symptoms. Would you say the same thing is for Alzheimer's? I think the amount of literature around blood sugar measurements in general and in particular A1C are very compelling. I mean, we've seen the A1C literature for at least the past 22 years. Yeah, that's pretty good. Interacting that Alzheimer's risk actually begins well below the diabetes range of A1C. People think, well, I got my A1C below seven. I'm gonna continue taking whatever the drug is. Getting your hemoglobin A1C below seven is fairly meaningless in the scope of trying to be as healthy as possible. We want to optimize everybody's markers so that they are at the lowest risk possible. So A1C around five is really great, 5.2 I can live with. But Alzheimer's risk really begins at around 5.8. A lot of people who are told, "Got your hemoglobin A1C is 5.8, you're good to go." That's in the normal range, it's not good enough. I certainly don't, I want it lower as do you. Is that your favorite test? I think it's a very important test. Mine might be fasting insulin level actually. Hmm, same one. It's predictive of where that A1C is gonna go in the future. So what would you want fasting insulin to be at? Three. Three, yeah, agreed. Yeah, where do you think-- Go ahead. Where do you think the GLP1 drugs are gonna fit into this equation?
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It's a fascinating story and this is certainly the topic du jour. And if we take a step back and sort of revisit our conversation that what is so central in what makes a good brain go bad is the shift in the brain's immune cells and what causes the shift in those brain immune cells is a shift in their metabolism.
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And their metabolism mirrors body metabolism. It's an interesting segue to the conversation about GLP1s, isn't it? Because we know that the GLP1 drugs are powerfully influential more than anything that we've ever seen in terms of metabolism. Therefore, one might assume that maybe there's a role for GLP1 agonist drugs in neurodegenerative conditions. Do I think there is or will be soon? And did I write that in my new book? I did. I absolutely did. And that may surprise people. Dr. Perlmutter's thinking about lifestyle and natural ways of doing this and that. You bet. Alzheimer's is almost uniformly a fatal condition, a lethal condition. By some it submits it's the third largest cause of death in adults in America. So would we consider the use of GLP1 agonist drug if in fact it were demonstrated to be effective in Alzheimer's? I absolutely would. I think the risk profile is acceptable in the face of a fatal condition. We would give dangerous chemotherapy to cancer patients because otherwise they would die. So that's the comparison. Well, let's look at what the data shows first of all. So in 2024, I think in April, the New England Journal of Medicine
\[00:24:52:18 - 00:27:18:06\]
was a fascinating interventional trial. It means it was a double blind placebo trial where they had a group of 151 Parkinson's patients. Half of them got a GLP1 agonist drug and the other half received a placebo injection every single day. And they followed these patients over the course of one year and they measured their functionality. And what they found was really quite interesting. In the placebo group, as one would expect, their functionality declined on what's called the unified Parkinson's disease radix-hale UPDRS. And that's what you see in Parkinson's. In the group receiving the GLP1 agonist drug that targets metabolism, that targets the microbial cells, their situation did not demonstrate any decline whatsoever. And as a matter of fact, there was a tiny improvement. Wow. Bart Simpson would say, "Cowabunga." I mean, it's breathtaking because look, we have drugs to treat Parkinson's tremor and rigidity and all those things that work very well, but that's only treating the symptoms. It's not treating the underlying issue. This was the first intervention that target the metabolism of the brain and the brain's microglial cells. And what was the response? It was phenomenal and it was breathtaking. To be fair, about 48% of the individuals who received the medication had gastrointestinal side effects. Some of them were in fact fairly compromised to the extent that they would have to stop the medication. But it opens the door, doesn't it? It's a glimmer of hope. That said, what do we know in Alzheimer's? Well, in looking at diabetes patients for which the GLP1 drugs were first developed, who are taking a GLP1 versus another type of diabetes drug. And there are several other types, including things like a metformin, et cetera. What was discovered is that when you follow these individuals, those getting the GLP1 agonist drugs had a 40% risk reduction for the development of Alzheimer's. And recall, these are individuals who are at great risk because they're having
\[00:27:19:07 - 00:27:37:09\]
where we give half the people placebo pill who are not diabetic and half the people, a GLP1 agonist drug, in this case semaglutide, who actually already have Alzheimer's and we will follow them over a period of time to determine is there any effect in terms of cognitive function?
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Well, this was done in multiple countries around the world, a very large study called the EVOKE and the EVOKE Plus study, what did they find?
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Well, the study did not reach its clinical endpoints in terms of showing any slowing in the decline of cognitive function. And that's what made all the headlines. Let's talk about what that means. But first, let me mention one thing that they did find that really didn't get much attention. A marker of inflammation called C-reactive protein was reduced by 30% in the treatment group in comparison to the non-treatment or placebo group. That's important because that is-- That is important. Inflammation is reduced, maybe we need to do a longer study. That said, this is an oral preparation of semaglutide, a large molecule, meaning two things.
\[00:28:27:18 - 00:29:06:00\]
Could it, because it's oral, not have made its way to the blood brain, through the blood rember into the brain, possibly? Is it because it is a large molecule in comparison to the one used in the Parkinson's study? Be another reason. So you can be sure that, and I'm telling you this is what's going on, there are multiple GLP1 agonist trials being done to intervene to treat Alzheimer's disease right now. There are multiple ways that really high tech is really looking at-- Fascinating. What we can do to the microglial cells to shift them back to being supportive,
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we can do it right now by putting you on a dietary change, increasing your physical activity, making sure you get a good night's sleep, increasing your social interaction, taking very specific supplements, some fairly novel ideas like flashing a light in your eyes at 40 times per second, some really cool things we talked about in the book that are right on the edge right now. They're actually being studied in humans by top institutions like MIT. Interesting. The point I'm making though
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is that we should be preventing and not waiting for the disease. Yeah. So maybe I won't go there. Let's concentrate on keeping everyone's brain healthy and as a side effect of helping reduce our Alzheimer's risk, for example, your brain day by day is gonna work better. Yeah.
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In your book, you quote a study, the Tansey study, I'm not sure if I'm saying this right. And I found it really interesting because they map out a lifestyle plan that can be very helpful for prevention. Can you dive into that study, tell us what it taught us and map out a plan for us for the person listening that wants to do it differently?
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And who wouldn't want to do it differently? Right.
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What Dr. Tansey and Dr. Dean Ornish did was they studied 51 individuals with existing Alzheimer's disease. These are patients with Alzheimer's who may have been told, "Hey, you know, you take the IV drug or that's the best we can do." But Dr. Tansey, Rudolph Tansey and Dr. Dean Ornish created an intervention that had, believe it or not, multiple inroads. It wasn't just one monotherapy, one type of- Yeah, it was really extensive. Yeah, but approachable. They changed- Agreed. They changed their patients' diets. They increased their daily exercise. They did stress modification. And their study of 51 patients over a 20-week period of time
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demonstrated findings that were fairly breathtaking. We would have expected these patients with Alzheimer's disease to decline on the tests of their cognitive function. No, that's not what happened. In 70% of these individuals, they either stabilized or they got improvement. That's amazing. There's never, ever been a drug that has even targeted improvement, much less brought it about. And who's heard of that study? You know, that's- Well, what- I dove into the study, because I love research. And what shocked me is that it was largely plant-based. Yes. Can you talk about that? Because we talk on this channel all the time. Carnivore, vegan, like everybody's arguing over high protein, low protein. And when I saw that, I was like, "Huh, okay. "What does that tell us?" What does it tell us? It tells us a lot of things. It tells us the power of the polyphenol. We'll talk about that in a moment. But it also tells us the power of dietary fiber. And it really begins to open the door to the so-called gut-brain connection and the brain-gut connection for that matter. The idea that I wrote a book about this many, many years ago called "Brain Maker." The idea that, who knew? Hippocrates knew. The idea that what is going on in the gut can influence the entire body. And here's the news flash. The brain is part of the body, who knew? So the idea that things going on in the gut are so influential in terms of brain health. The fundamental issue that connects the brain to the gut, I think more than anything else, is the process of inflammation. When our gut bacteria, in terms of their diversity and functionality, is threatened, then we increase the permeability, the leakiness, if you will, of the gut lining. Bad things get out into the systemic circulation and even locally in the gut, right in the gut, target certain receptors that increase ultimately, inflammation. Those chemicals of inflammation that are called inflammatory cytokines, cytosale kind means they move around, make their
\[00:35:44:20 - 00:36:36:08\]
The fundamental issue that is gone awry is their metabolism. And I've mentioned that before, when their metabolism shifts, that is what characterizes them becoming destructive. And the key player in their metabolism is the function of their energy producers called the mitochondria. So in a very real sense, what is upstream of all of these issues, of all the neurodegenerative conditions, of lack of hormone functionality in menopause, of cardio metabolic conditions, cardiovascular disease, all chronic degenerative conditions of the body, that the World Health Organization ranks as the number one cause of death on the planet are fundamentally issues with how the mitochondria are producing energy.
\[00:36:37:08 - 00:37:59:14\]
When the energy production of the mitochondria is compromised, that signals the cell, the microglial cell to become threatening. Now that's the understanding that allows us then to target the mitochondrial oxygen. One specific thing, right. Bring them back to being supportive. That's where things like hyperbaric oxygen and a ketogenic diet. I'm just going to ketones. I'm like, where does ketones fit into this? Oenzyme Q10. All of the things that nurture and support mitochondrial function are the players that are so valuable for brain health and keeping these brain immune cells, the microglia, in their supportive phenotype and even shifting the ones that are not supportive anymore back to being supportive. That explains why Dr. Tanze and Dr. Ornish's study was so powerful. What did they do? They put people on a lifestyle program that ultimately improved energy production and convalescent in the body and brain. And reverted their microglia back to being supportive. Now you get it, it all makes sense. It's just a target. The mission for me is challenging because it's a little complicated. It's not like, okay, go to the doctor now that you're cognitively impaired, sit in a chair and get an IV.
\[00:38:01:03 - 00:38:42:04\]
I would do that. I recommend that if it worked, it doesn't work. So it takes a little bit of doing to unpack everything we've opened up so far. We've got a lot more, I think, to flesh out because it's up to us to make those changes. Is it work? Yeah, it's a little bit of work. Is it worth it? You bet it's worth it because you don't wanna be that person. You don't wanna be in that situation where I just had my cognitive analysis and hey, it wasn't right. It didn't come out great. It's too late. I kinda knew it wouldn't because I noticed I can't remember my grandchildren's names, the wifi code, I go into rooms, I don't know why, all of these things. By the time those things are starting to happen,
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we're already deeply down the continuum. That's not where it starts. It starts with your metabolic challenges in your 30s and 40s.
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So one of the guests I've had on here over the, I've actually brought her on twice, is Dr. Georgia Edie. Do you know her? I do very well. I had her on the podcast. Yeah, so she just came out with an expert consensus talking about sustained ketogenic diet for chronic depression, anxiety, and schizophrenia, I think was one of the things they looked at. And she's really trying to infiltrate the idea that ketones, especially continuous ketones, throughout the body and brain can reverse some of these conditions. Can you talk a little bit about, because my audience, we get ketones through fasting. That is the way that so many people access the ketogenic system. So where do ketones fit into this? And is it all internal ketones? Can we use exogenous ketones to help this kind of condition? So first let me say that the issue here and what she's talking about, the neuropsychiatric issues that are targeted for this type of intervention or becoming, or going into ketosis is all about energy. It's all about energy production from the mitochondria. A wonderful book called "Brain Energy," dealing with mitochondrial function by Dr. Christopher Palmer explores this in great depth. So the idea of being on a ketogenic diet to give those mitochondria better fuel such that they can produce energy much more efficiently, I think is absolutely fundamental to the idea of reverting the microglia back to being supportive. So what are the interventional trials looking like? Well, there are several interventional trials now done with patients who have existing Alzheimer's and also existing, not the same patient, Parkinson's, done by Dr. Matthew Phillips. I've had him on my podcast a couple of times. The results are profound. I mean, when you provide energy to the brain in the form of ketones by dietary restriction, by caloric restriction, by time restricted eating, certainly by restriction of carbohydrates and increasing dietary good fat,
\[00:41:10:08 - 00:42:40:13\]
it has powerful effects in terms of the energetics of the brain. But all of the discussion until now has focused on the fact that neurons, the brain's cells, need a lot of energy. Well, neurons are only 50% of the brain cells. We've got a lot of other cells in the brain. As a matter of fact, these microglial cells, brain immune cells represent 10% of the brain cells. And who knew? They use energy too and a lot of it. If they can't make energy from their mitochondria, they become threatening and they destroy the brain. This now lets us understand finally why the diabetics have increased risk of Alzheimer's disease. Why energy, why anything that threatens availability of energy is associated with increased risk for the development of Alzheimer's disease. The risk is increased with elevated, you mentioned it, waist to hip ratio, a metabolic issue, certainly with head trauma, with stress that is increasing inflammation in the brain. We talked about how these cells see that inflammation and say, oh, danger, I'm gonna shift to being the evil, call out the fireman because we've got trouble. So for me, before we went on the recording, you asked me a question, why this book and why now? And what does it mean to me? It explains everything I've done for decades. I wrote Grain Brain in 2012.
\[00:42:41:16 - 00:44:47:21\]
And what we talked about at Grain Brain was, yeah, as a matter of fact, eating a diet in highly processed carbs is associated with a bad outcome for the brain. As a matter of fact, in that book, I actually have a graph getting back to a question you asked earlier demonstrating Alzheimer's risk plotted against the A1C. Then I wrote that in 2012. And back then we didn't have the term, which is now in vogue called ultra-processed foods. That term hadn't even been invented. We called it Western Standard Diet. Yeah, well, yeah, first it was Standard American Diet, the Western diet, and now it's the global diet, call it like it is. Right, right. It's typically globally, unfortunately, which is why global rates of these brain degenerative conditions are skyrocketing in lockstep with the changes in metabolic health, with rates of diabetes, for example. So again, it explains what we talked about in Grain Brain that when you consume those foods, and now it's validated. Last year, a study came out in the Journal of Prevention of Alzheimer's, the Journal of Prevention of Alzheimer's. Wow, such a journal. I mean, when I used to talk about preventing Alzheimer's, it was people, not everybody was supportive. I'll leave it at that. I certainly won't name names. But anyhow, when you look at these ultra-processed foods, this study came out and followed 1,111 individuals for 12.7 years, average age, I think was 69.5 years. And these were individuals who had already some metabolic issues, some insulin resistance, elevated blood sugar, obesity. These people are prime for cognitive decline, if not the development of Alzheimer's. Right, right. And what they found was in following these individuals, again, over a long period of time, 12.7 years, that averaging one serving per day of ultra-processed foods was associated with an increased risk of developing Alzheimer's of 13%.
\[00:44:48:23 - 00:45:08:17\]
Wow. If you consume-- Just one meal, one meal a day. Not even a meal, I'm talking about a serving, a handful of chips. If you consume 10 or more servings per day, and that is exceedingly common, when you consider that 60% of the calories that Americans consume, adults, are from ultra-processed foods, that's sobering,
\[00:45:09:21 - 00:49:14:04\]
if you consume 10 or more servings a day, your risk is tripled for a disease for which we have no meaningful treatment. So, gosh. (Laughs) So the food industry has once again destroyed us. Yeah, it's what, again, I don't wanna curse the darkness, I wanna light the candle. So let's talk about what we can do, we can change our diets. I explained it in the book, "How to Eat." And you're right, vis-a-vis Rudolph, Tanze, Dean, Ornish, and others, it's plant forward for the reasons that we've already talked about. Because the fiber, I just want my audience, because the fiber, I've been really on a fiber kick recently, and because everybody got so into protein, and I really feel like it needs, it should be called a fiber-forward diet. I would agree with that, and by all means, I'm not suggesting that everybody needs to be vegetarian. Right. I am not suggesting, I am pleading that there's a lot of plants on your plate, and they are colorful, so that we get a variety of polyphenols that are wonderfully supportive of the gut microbiome, that target our gene expression, that have a role to play in the modulation of our epigenetic markers, as was recently demonstrated and studied by Dr. Austin Perlmutter, our son. You know that guy. Yeah, he did an amazing study on one particular intervention, using something called Himalayan Tartary Buckwheat, which is really rich in these polyphenols, showing a profound effect on epigenetic age markers, in this case, a marker of the rate of aging, that's called the Dunedin methylation clock. But, you know, and Austin has another study coming out very soon, with a much larger population doing a lot more in-depth evaluation of this intervention, in terms of, you know, what this Himalayan Tartary Buckwheat can actually do. Yeah, and so back to the ketone, because in all the research I've done on fasting and the ketone, I gotta ask more on this, because Lisa Moscone, who I also interviewed, said that the brain is much more receptive to ketones,
\[00:49:15:13 - 00:54:32:03\]
and so many others, Dominic D'Agostino, wonderful researchers that are just Matthew Phillips doing such great work demonstrating that, hey, this is a tool, and it happens to be a very, very powerful tool. From my perspective in the new book, this is a tool that reestablishes metabolism in the brain Exactly. that through the term immunomatabolism targets our microglial cells and can revert them back to being brain defenders. Yeah, I mean, I watched the tens of thousands of comments even here on YouTube over and over again about a woman who starts to learn how to just intermittent fast, just a small fast, and she starts to eat whole foods, and yes, she loses weight, but the second most common thing is that her brain gets back on track. The brain fog goes away and the clarity comes back. Can you help my audience understand, when you talk about brain energy, why is a ketone a more clean source of brain energy than a glucose molecule? Well, I think that the issue has to do both with the molecules, but I think more importantly, deals with the down, the fact that if you're powering your brain solely with glucose, and your diet is one that really amplifies glucose, you're setting yourself up for disaster. Right. And that does not happen on a ketogenic diet, or when you're occasionally in ketosis. When you're occasionally in ketosis, you're reducing the functionality, you're reducing inflammation that challenges brain metabolism, and allowing all brain energetics to improve, but let me reemphasize an important point. The focus of the brain energetics has always been that the neurons work better when their energy production is rock solid. I get that, I get that, but it's time that we make a bit of a pivot to include the idea that the brain's immune cells that are pretty much in charge of your brain's destiny really depend on good energetics as well. So, there's a book by Kasey and Callie Means called "Good Energy" that really nails this down in terms of mitochondrial function
\[00:54:33:04 - 00:58:21:18\]
Memory loss, metabolic issues, loss of executive function, and who knew? Loss of smell. Yeah. So is it loss of smell one of the first things? It may be in many people. Yeah. And so why would that be? Now we get it. We understand that this manifestation of this metabolic challenge to the brain that you are absolutely correct in stating can be improved as we utilize this type of intervention called getting into ketosis. And we don't have to be full on ketotic all the time. No, no. And where does exercise fit into this? Cause I did a lot of research from my last book, Age Like a Girl on BDNF and how powerful it can be for neuronal growth. And you can get BDNF through weightlifting by breaking muscles down. It sends a metabolite up into the brain and starts to stimulate that production. So where does strength training fit into this? Yeah, it's fundamental. I mean, it's critical. So I mean, here's this BDNF brain derived neurotrophic factor that you just described, acting just like I mentioned insulin works. It is a trophic hormone. This is a chemical that tells neurons to grow. It stimulates the growth of new brain cells. Who wouldn't want that? That nurtures the synapse where one brain cell through its dendrite connects to the next neuron. And even the growth, the enhancement of the formation of synapses is so critically important for learning. And this was first demonstrated by Dr. Kirk Erickson in the late 1980s, where he did a study measuring through MRI analysis, the effects of exercise versus simple stretching over one year period of time in individuals, looking at the size of their hippocampus, their brain's memory center, the growth of these new neurons actually happens. One other area, but let's talk about the brain's memory center. And showed that in the intervention group doing the exercise, their hippocampus didn't stabilize in terms of declining with age. It increased in its size, as did improvement in memory function. So this has now become something that
\[00:58:22:20 - 00:59:09:19\]
It's critically important. Yeah, the aerobics are important. Matter of fact, one recent meta-analysis of 36, I think, different studies, revealed that it was the combination that was most brain beneficial. It wasn't just aerobics, it wasn't just weight training, but it's both, especially in the 65 plus a year old category. These are the individuals who benefited most. Yeah, yeah. So, one of the ways I like to look at books is I think they open up a cultural conversation and they start to change the direction of the way we think, the way we interact with our doctors, the way we interact with each other. What do you think and what are you hoping this book will do as far as the cultural conversation goes?
\[00:59:11:18 - 01:00:43:06\]
Well, we're faced with some powerful messaging that tells us otherwise. Right. It's telling us eat whatever the heck you want and sit on the couch, binge watch, doom scroll, and we got this. Offload your agency for your health to someone, something else, right? Yeah. This idea that-- Somebody will save you. You bet. And the idea of just hope for the cure. Well, James Cameron, the movie director, famously said that hope is not a strategy. And I want people to hear the other side of the story that I would absolutely 100% embrace an Alzheimer's drug. If one were safe and effective, you'd hear me singing its praises. You heard what I said about GLP1, so I keep that door open. We're watching the research. We're still watching that. And when it looks compelling, I'm gonna be singing its praises. Not for everyone, not as necessarily right now as a preventive, but in the case of diagnosed Alzheimer's, if it's proven to be effective, you bet. I will count me in. And again, that surprises some people right now, raising their eyebrows, but my mission is not to be always thinking outside the box. I think the mission is to make the box bigger. Yeah, it's beautiful. That we are inclusive, integrative, looking at all inroads to better health and in this case, better brain health. So what am I hoping?
\[01:00:45:00 - 01:01:19:07\]
I'm hoping that people ultimately walk away from reading this book with the firm understanding that they can change their brain's trajectory beginning today and not to outsource your brain's destiny to somebody who's trying to make you believe they've got an answer. Yeah. If you were to consult a woman who, let's say a 50-year-old woman who is trying to get her health on track, what would you tell her as the most powerful lifestyle tool she has?
\[01:01:20:12 - 01:01:24:10\]
It would be belief that you can do it. That's the most powerful. Ooh, I love that.
\[01:01:25:22 - 01:03:00:00\]
Because if you don't, nothing else matters. You're not going to do anything else. You're not gonna change your activity level, diet, time you spend in nature, the quality of your sleep, that you can change the quality of your sleep by doing certain things. We talk about them. You've talked about them before as well, or had guests as well. Now, caffeine curfew, what time do you exercise? Getting off your computer at night, getting bright light in your eyes in the morning, all the things, right? Right. They matter a whole heck of a lot. They do matter, yeah. Am I in favor of metricizing, of measuring, of biometrics, of the wearables, as it were? Absolutely I am. How else will you know? How else will you know how well you slept last night if you're not able to measure it? And gosh, we live in a time, not only can you determine how long you slept, but what is the quality of that sleep as well? How much deep sleep did you get that activated your brain's glymphatic system to clear out the debris? How much REM did you get to consolidate your memories? How long did it take you to fall asleep? And did you awaken several times during the night that you may not remember doing? These are really important things. And gosh, whether it's your Apple Watch, your Oaring, your Whoopa, whatever it may be, these are available to all of us. And as a race to exercise, it's very expensive to go out and buy the equipment. No, you can buy a new pair of what used to be called sneakers and give it a go. That's all I'm asking. You can use your own body weight to exercise. Maybe buy some resistance bands.
\[01:03:01:07 - 01:03:37:20\]
Right now, as you see, I'm living on a boat. And there is a gym nearby, that's great. But when we're out, resistance bands, we're wonderful. TRX, another way of using your own body weight. There are ways of making this happen, but you gotta not just wanna do it, but understand why you're doing it. And why you're doing it right now today is that 20 years, 30 years from now, we'll be having a different conversation because your brain is doing really, really great. And you did all those things, terrain in your metabolism, that will help your hormones function appropriately, help you with menopause.
\[01:03:38:21 - 01:04:13:08\]
If you're a lot younger, it'll stabilize your menstrual periods, it'll help you lose weight, it'll help your cognitive function now. When you're in your 30s and 40s, who wouldn't want that? When you're in your teens, when you're in your adolescence, why wouldn't you want that? Yeah, yeah. Well, this was fascinating. I really appreciate what you're up to. And I wanna make sure everybody gets the books. Where can they find the book? And how can we support you? Well, here's the book. I just got my hard copy a couple of days. Brain Defenders, I love the- Of the-
\[01:04:14:12 - 01:04:35:23\]
It's gorgeous. The graphics. Anyway, so the website for Brain Defenders is braindefenders.com, who knew? There's all kinds of bonuses at that website when people buy the book. Buy the book anywhere you want. I mean, it's been acquired by 16 countries around the world. So it's- Amazing. It's getting some attention, which I think is great.
\[01:04:37:03 - 01:04:52:01\]
For me, I'm at DR, as in drpearlmutter.com. That's my website, drpearlmutter.com. Just did a whole new website. I'm really excited about that. Oh, exciting. Yeah, so again, braindefenders.com. That's a fun project. All the places that people might buy a book,
\[01:04:53:01 - 01:05:20:20\]
you'll find it there. Yeah, amazing. Well, Dr. Pearl Mutter, what an enjoyable conversation. And I hope this book just permeates the culture and really gets people motivated for prevention. So thank you for everything you do. Yeah, and thank you. I appreciate the opportunity to spend time with you and just to have this platform for getting out this information that I feel is so fundamentally important. So thank you for that. My pleasure. I appreciate you.
\[01:05:22:19 - 01:05:39:17\]
Thank you so much for joining me in today's episode. I love bringing thoughtful discussions about all things health to you. If you enjoyed it, we'd love to know about it. So please leave us a review, share it with your friends, and let me know what your biggest takeaway is.

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