The Melanie Avalon Biohacking Podcast Episode #108 - Dean & Ayesha Sherzai

TRANSCRIPT

Melanie Avalon: Hi friends. Welcome back to the show. I am so incredibly excited about the conversation that I am about to have it is with a topic that affects so many people and I think that we don't realize it affects so many people. The stats that I learned on this topic, the guests that I have today, reading their books really just blew my mind. That is the topic of Alzheimer's. Even beyond that dementia, brain health, memory formation, what makes things go wrong, it's really, really a huge topic affecting so many people and I'd been wanting to do an episode on the subject for a long, long time and then I actually got approached by, I'm just so incredibly honored, the codirectors of the Alzheimer's prevention program at Loma Linda University, Dr. Dean and Ayesha Sherzai. 

They have two incredible books I read both of them. One is The Alzheimer's Solution: A Breakthrough Program to Prevent and Reverse the Symptoms of Cognitive Decline at Every Age and then their newest book, which is The 30-Day Alzheimer's Solution: The Definitive Food and Lifestyle Guide to Preventing Cognitive Decline. Friends, I read this book. I learned so, so much not just about Alzheimer's in dementia, but the brain, how the brain works, how things go wrong, it's fascinating, it's mind blowing. I am just really, really excited to jump into this conversation. So, Dean and Ayesha, thank you so much for being here. 

Dr. Ayesha Sherzai: Thank you so much for having us, Melanie. We're so excited to be here. 

Melanie Avalon: To start things off, you talked about this in your books, but I was wondering if you could tell us a little bit about your personal stories and what led you today to where you are with your focus on this issue. 

Dr. Ayesha Sherzai: Absolutely. We're husband and wife. We've been together for about 18 years now, and the day we met, our conversation started around our grandfathers. We both had two grandparents each who had suffered from Alzheimer's disease and as children of parents and being a part of the family that included them in their environment, we grew up with them being a big part of our lives. They were both our heroes. We learned a lot from them. They instilled all the important values of life in us. So for us, they were role models. We also had the privilege of being with them for a long time.  

So, seeing them lose bits and parts of themselves for this disease was one of the most painful things that we experienced and our parents experienced. In many ways, even before we went into medicines, we were essentially caregivers for very amazing, incredible people with Alzheimer's disease and that left a mark. So, we shaped our lives in a way where we wanted to get into the research of neuroscience to understand the brain better. When we went into the field, we were hoping to find a treatment for it so that we could help people not go through that pain that we observed in our parents. That evolved into a much bigger plan. Now, our lives are focused in to not just seeing patients in the clinic in the hospital but to disperse this message of hope that devastating diseases like Alzheimer's can be prevented if it's instilled early and in communities. 

Melanie Avalon: I love hearing that so much. I love when things come from a personal background like that to make change. I would love to go deep into the science but I just have a question about the subjective experience of Alzheimer’s because I imagine unless you have it-- I was thinking about this. I imagine unless you have it, it'd be really hard to grasp what that would be like, but when people start getting dementia and/or Alzheimer's, and maybe we can explore the differences there, you realize you're getting it. Then at some point, do you not realize you have it anymore? I don't mean this as a joke, but could I have Alzheimer’s right now and not realize it? 

Dr. Dean Sherzai: Great, great question. First of all, let's differentiate between dementia and Alzheimer's. Dementia is the umbrella category. It's basically when somebody is having cognitive deficits to the extent where they can't do one of their daily activities, be it driving, their finances, cooking, answering phones, or taking care of medications, any one or many of those. Not because of physical limitations, but because of thinking limitations, cognitive limitations. That's dementia. So, it's an umbrella category. There are many types of dementias, frontotemporal dementia, Lewy body dementia, Parkinson's dementia, PSP, multisystem atrophy, Huntington's dementia. But the biggest one is Alzheimer's dementia, which is 60% to 70% of all dementias is Alzheimer's dementia. At the beginning, they have some distinct features and the pathology behind them are a little bit different. But as the disease progresses, they all start looking the same, because they start devastating the entirety of the brain. The onset is important. 

Now, the next element that you ask is how do we know when we have it? Well, I tell people assume you have it because Alzheimer's is not a point. You don't develop Alzheimer's at a point. It's a journey. In that journey, whether you're avoiding the traumas or the negative effects on the brain, and whether you're accumulating the reserves to withstand life's traumas, that determines whether you go over the edge or not. But the journey is throughout life. I tell people assume you're at risk and you're in your 20s and 30s not in a negative way. I actually look at that as empowering. Because the flip side of dementia and Alzheimer's is avoiding dementia and Alzheimer's, and building better brain throughout life.  

Alzheimer's is not driven by genetics. Only 3% of Alzheimer’s is driven by the genes that are 100% penetrant. Meaning, that if you have those genes, no matter what you do, you'll get the disease. Only 3% of Alzheimer’s. The rest of Alzheimer’s, yes, has a genetic component but it's an interplay between genes and environment, and that environment dominates. Environment and lifestyle dominate. That's the factor. That's the hope. That's the fact that we can do a lot about it and that's where the power is in everybody's life, in their homes, in their communities, and in work. And here's the thing. You don't have to buy a single thing from us, from anybody else, no protocol, no, nothing. It's a comprehensive lifestyle though. You can't fix it with just blueberries. You can't fix it by little pill here and there. Blueberries are great, but don't get me wrong.  

Melanie Avalon: Oh, I love blueberries.  

Dr. Dean Sherzai: Yeah.  

Dr. Ayesha Sherzai: Let's just save the blueberry-- [crosstalk]  

Dr. Dean Sherzai: Yeah, for some reason, this is my month of attacking blueberries. Blueberries are awesome. But I want people to know that, they go eat the burger and then they say, “Oh, I had some blueberries.” That's not going to do it. It has to be very comprehensive, which our neuro program, which is all of those things and it's what you do at home on a regular basis and around habits. I think where we are a little different is twofold. Of course, we've done that research at Columbia, and NIH, and all of that stuff, but what we did early on is transition to translation. Meaning, translation of the research into people's lives. In fact, we were the first and in fact, even now, there's nobody that does it at the community level. We currently lead the largest brain health community initiatives in the country, just the two of us. In beach cities, and African American churches, and other places we're starting throughout the country. It's not a gimmick. It's a comprehensive approach to brain building which, by the way, helps you avoid Alzheimer's, dementia, stroke, all of those things. 

Melanie Avalon: I love that so much. I'm full of so much hope. On blueberry front, I literally eat pounds of blueberries. I'm not kidding like pounds. 

Dr. Dean Sherzai: Yes, yes.  

Dr. Ayesha Sherzai: Oh, same. 

Dr. Dean Sherzai: Yeah, we love it, too. We love it.  

Dr. Ayesha Sherzai: Yeah, my blood is just blue.  

Dr. Dean Sherzai: Yes, yes.  

Dr. Ayesha Sherzai: Because of all the blueberries I eat. 

Melanie Avalon: I love blueberries. I have a really quick question. So, the 3% of people where it is genetic is completely unavoidable in that case or even in that case is it--? 

Dr. Dean Sherzai: Yeah, even in that case, which is three genes, presenilin 1, presenilin 2, and APP.  

Dr. Ayesha Sherzai: Amyloid precursor protein.  

Dr. Dean Sherzai: Penetrance means the amount of influenced by the genes. Those are 100% penetrant genes. Meaning, that they have profound influence on outcome. Huntington's is a similar disease. If you have that gene, that little abnormality on chromosome four, no matter what you do, you're going to get it. Now, in those three genes in Alzheimer's, lifestyle still affects it. In fact, we looked at APP which is actually on Down syndrome, people who have Down syndrome, if they live to age 50, they almost universally develop Alzheimer's because their chromosome 21 is threefold, triple chromosome 21 and the APP gene, which could produce as amyloid is on that gene. So, you're getting excess amount of amyloid. But even in that population, when we looked at the data at NIH, we saw that lifestyle had an effect on even that population. But the other 90% plus, yes, they're genetically driven like APOE4 and others but those genes are not 100% penetrant. In fact, they're literally a relationship between lifestyle and gene. So, if your lifestyle is good, the genes don't have as much effect and there are multiple studies including our own that have shown that. 

Melanie Avalon: Can we paint a picture of what is actually happening in the brain with dementia and Alzheimer's? You keep mentioning amyloid but what's difference between the amyloid and the tau protein, and what is actually happening in the brain? 

Dr. Dean Sherzai: Yeah, the amyloid and tau are proteins that go abnormal proteins that one sees in those diseases and it’s like Alzheimer's, disease like Parkinson's. It's another protein which is synuclein and others as well. We know that those start being abnormal early on, 10 to 15 to 20 years early, but we don't think that those are the drivers. They are downstream outcomes. What drives them the most is the vascular and inflammatory outcomes. There are four pathways that we've identified. Oxidation, inflammation, glucose dysregulation, and lipid dysregulation. 

Lipid dysregulation means the fat levels. Lipid levels go abnormally high or your genes or your proteins are not able to process those fat molecules well. One of the other genes that have been associated with Alzheimer's is APOE4. It's actually one of the more common genes. If you have one gene from one parent, your risk goes up four times. If you have two genes, one from each parent, your risk goes up 12 times. Does that mean that if you have two genes, which is only 2% of population, if you have two genes, you're going to get Alzheimer's? No. Nearly 50% of people who have two APOE4 genes never develop Alzheimer's. Now, let's look at that gene. What is that gene 4? APOE4 codes for a protein that helps transport fats from cell to cell from organ to organ. So, if you have APOE2, you have a really good protein. It does its job so well, people with APOE2 are actually excessively protected against Alzheimer's. APOE3 is a wash but APOE4 does its job poorly, so you actually have a much higher risk of Alzheimer's. If it's a lipid transporter gene, and some people don't develop and why? Lifestyle. They have better controlled fats, and lipids, and triglycerides. So, that's one pathway, lipids. 

The other was glucose, or diabetes, or pre-diabetes. We did a nationwide paper research project on pre-diabetics. Not even diabetics, prediabetics. And even prediabetics were at greater risk of dementia. So, what is that? Glucose dysregulation. In other ways, inflammation. Inflammation is very common. People who have inflammation as a result of joint problems or gingival hyper inflammation like people who don't take care of their oral hygiene or head trauma. All these inflammatory diseases, that really increases your risk of dementia. Then, oxidation as well, which comes from food, and fat, and things of that nature, or toxins.  

If you take care of those things, guess what happens? Your risk goes down significantly and the things that determine those four factors are food, exercise, stress, and by food, I mean food and toxins such as alcohol, and toxins, and cigarettes as well. So, food, exercise, stress, and sleep. Those four factors are so pivotal in affecting these processes that we know that as much as 90% of Alzheimer's can be prevented. That's remarkable. When we said this a few years ago, we would not even be invited to talks but now everybody's accepted that the numbers vary, some people say 50%, others say 60%, we say 90% if it's optimal, but everybody agrees that Alzheimer’s for the most part can be avoided. 

Melanie Avalon: Those four pathways, the lipid dysregulation, glucose, oxidation, inflammation, is it the effects of those lead to or encourage the amyloid and tau buildup, and that is still what actually causes the dementia? 

Dr. Dean Sherzai: Yes and no.  

Dr. Ayesha Sherzai: Yeah.  

Dr. Dean Sherzai: They promote amyloid. Yes, subsequently, amyloid tau as well. But in themselves, actually, more commonly, they themselves significantly affect the outcome. 

Dr. Ayesha Sherzai: That's the thing over the last few decades. The reason why we have very little hope of finding one treatment for Alzheimer's disease is because everybody at NIH and in the world of science have been focusing on amyloid, the downstream effect. We know that there is an abnormality of amyloid beta protein clearance versus production. Either, there's too much production or there's too little clearance of that bad protein that causes damage to brain cells and their connections. Same goes for tau. But what causes that imbalance? It's multifactorial. It's not just inflammation. It's not just oxidation. It could be a combination of different things or all of them in some people. That's why people come to Alzheimer's or they manifest Alzheimer's based on their specific risk factors. 

You have very healthy people who are runners, who relatively eat well but then they have incredible high amounts of inflammation because they're not getting enough sleep. Or, you have somebody who's had multiple head traumas throughout life, but they live healthy otherwise. There you go. That increases their risk of developing Alzheimer's disease. You have somebody who has no stress, sleeps really well, but their food is just horrible. They will develop Alzheimer's disease through different routes. It's a very multifaceted, multifactorial, bigger picture. I'm happy to hear we're happy to hear and see that, finally scientists have realized that it's almost impossible to find one treatment, one medication, that it has to be a very complex approach to this disease is not one disease. It's multiple different things happening in the brain at the same time. 

Melanie Avalon: Wow. It sounds like the search for a universal cause of aging, but nobody can really agree. There's all these different hallmarks which seem to overlap a lot with the four that you outlaid for Alzheimer's. 

Dr. Dean Sherzai: In many ways, you're right. Yeah, those four pathways are not just for Alzheimer's, but for other diseases as well. But why Alzheimer's? Because the brain, this little three-pound organ, 2% of the body's weight, consumes 25% of body's energy at any one point. So, it's overwhelmed all the time. That's why the effect on the brain is probably significantly more than any other organ in this system. 

Melanie Avalon: Yeah, another fact that I learned about the brain your book, what is the significance that the brain is a vacuum in the progression of the disease? A closed system?  

Dr. Dean Sherzai: Yes, the brain is contained in this structure called the blood-brain barrier. The blood-brain barrier are these endothelial tight junctions or tight connections around the blood vessels, around the brain that were very little can get through the blood-brain barrier, unless, it's either through active transport, or it's so small that it can get through. This hermetic environment is susceptible, because if toxins build up, it can cause significant damage. If clearance is not good, it can cause significant damage. In fact, when they've looked at-- Let me give one example. Lack of sleep. One night's bad sleep has shown to actually accumulate amyloid protein or other inflammatory products in the cerebrospinal fluid significantly. The nature of it being so active, so vascular, so overproduction of byproduct, and then it's closed system as well, makes it even much more susceptible. 

Melanie Avalon: It seems like it would be self-perpetuating in a way. It would be harder to climb out of once that spiral happens, or is it easier? 

Dr. Dean Sherzai: No, no, I agree with you. There are people that actually make claims that they can reverse Alzheimer's. We're not going to name names, and we were told that if we just hinted at the fact that we could reverse Alzheimer's, we would sell millions more books. We said that's unethical, we can't. There's no evidence that once fulminant Alzheimer's is on board, that you can reverse it. Be it with some little vitamins or even a comprehensive approach, you can potentially slow it down a little, but you can't reverse it, because the damage is so overwhelming, and that what you just described, which is this circulating pathway that gets accelerated is so rapid that it's impossible to reverse it. 

Dr. Ayesha Sherzai: Yeah, and some doctors are banking on the concept of neurogenesis, which means reproduction of neurons in the brain. It's something that hasn't really been studied extensively and even though it happens, it doesn't happen on a massive scale. We see evidence of that and examples of that in patients who have had strokes. Stroke is a condition when there's a blockage of an artery in the brain and part of the brain that doesn't get oxygen and nutrition, it dies. After a short period of time, the cells, the macrophages actually eat away that part of the brain and you're left with a hole in there. People have studied the process of angiogenesis and neurogenesis, and it's still at its very experimental process. Like Dean was saying, once the infrastructure is damaged to a great extent, it's impossible to regenerate that and that's why we don't see much change in advanced Alzheimer's disease with anything including lifestyle. 

Dr. Dean Sherzai: But that's not hopeless. Every year, one person is diagnosed with Alzheimer's every 64 seconds in the United States. That's actually an understatement because in a lot of communities, people get dementia, but they say, “Oh, it's just part of normal aging," they'd never report it. But if we can stop that conversion, it would be the biggest public health service ever. If we can slow that process down, that's a biggest public health service. We say 90% of it can be avoided. Let's say 40% of it, it can be avoided. Let me tell you why that's so important. We know the human cost. Earlier, you said that that, what's happening to the person themselves? I'll describe that in a second because I've actually having seen 14,000 patients, I have a sense because I've heard the stories at different stages, and I'll tell you that in a second.  

But let's talk about the cost. The human cost is just overwhelming. The financial costs. The second costliest disease in America is heart disease at $120 billion. Third costliest disease or disease is all cancers combined at $70 billion. Alzheimer's costs, direct cost $305 billion, indirect costs another $240 billion, that's more than $540 billion a year. That number is going to climb to anywhere between $1.1 to $3 trillion total cost by 2040, 2050, which will overwhelm our system. So, we really have to take it seriously and approach it a different way. And then, the human cost is even worse. What I saw it in my grandparents and Ayesha in her grandparents, specifically, my grandmother was the one that was-- Well, my grandfather was a brilliant, brilliant man and we would all gather around him at this farm that we had in Maryland. We would be playing chess all the grandchildren with against him and one day, he forgot how to move the night. That was mind blowing for the rest of us. But for him, we saw the fear just accumulate. Of course, he was trying to stay gracious and grand but you saw bits and pieces of him abating and going away.  

My grandmother took the other path, which is complete avoidance. The two pathways are fight or flight, hers, this brilliant matriarch, basically, turned her face from the world to actually face the wall out of fear. This is what we're fighting and that's why we're so adamant and so aggressive about gimmicks and charlatans because the families out there, they don't need any of us.  

Dr. Ayesha Sherzai: They're devastated.  

Dr. Dean Sherzai: To be honest, they don't even have to buy our book. But they have to approach it in a comprehensive lifestyle way and they don't have to pay anybody as far as vitamins or concoctions. This is a critical point. 

Melanie Avalon: Wow, that is incredibly haunting. So, is the cost of it because they require so much care? 

Dr. Ayesha Sherzai: Yes. So, that plus others. It's a chronic disease and usually, people live with memory problems for up to 12 years. That's just an average number depending on other comorbidities that they may have. We have a very broken system of how we're addressing patients with dementia. Back when we were training, when we went into the field, it would be essentially, the doctor seeing the patient, examining them, getting some MRIs, and some memory testing, and then giving them the news that they have Alzheimer's disease, that this was going to be a devastating condition, long term, and essentially asking the patient and their families to make the serious decisions for their life later on. I remember one of the worst experiences of my life was working in a clinic where there was a stack of nursing home brochures on the table, and the doctor would just slip one to the patient and say, “You better start making your plans right now, because you're going to have difficulty making decisions for yourself very soon.” And that's it. That's it. They would go out with all that fear and anxiety, little support, actually no support whatsoever, no medication to treat it, no medication to slow it down, and that's it. I'm glad that has changed now because we know that people can do so much before they can get to that stage and even if they are, they can do a lot to slow down the progression of the disease.  

Melanie Avalon: Speaking up on the medication prompt, because you do talk in the book about the medications that are available and why they don't exactly work, just hypothetically, if there was a medication, and I know we're on that the diet and lifestyle train, which is incredible, but just in theory, what would a medication have to do to actually work?  

Dr. Ayesha Sherzai: Yeah, that's a great question. We've learned a whole lot about medications and the biochemistry of-- Specifically, let's stick to Alzheimer's, because different types of dementias have different biochemistry and processes. For decades, scientists and NIH was focused on getting rid of amyloid beta protein, and they would support research that would just attack amyloid with different compounds in different ways. But they've realized that that's something it's almost like when the fire burns down the house and you get all the burnt bricks around you. The research on Alzheimer's was essentially, if I could paint a picture, was getting rid of the burnt bricks. Nobody really did research on how the house burned down and where the fire started.  

Now, people are actually not looking at that model or looking at multiple different models at the same time. Even large pharmaceutical companies like Pfizer withdrew their entire research project from Alzheimer's disease because they realized that they were looking at it in a wrong way. Close to maybe 400 clinical trials over many, many decades hasn't resulted in a single therapy. Not a single therapy whatsoever. There's some exciting research going on. Every year when we go to the Alzheimer's Association Conference, we learn more about nuanced research, personalized research finding out individuals, what do individuals carried their genes, their biological risk factors, their metabolic risk factors, and coming up with a therapy in that realm. So, I think I'm speaking for Dean, we think that there's not going to be one medication. There's not going to be one infusion. There's going to be multiple things that a patient has to go through for a treatment, whether that's immunotherapy, whether that's controlling the internal biochemistry of an individual, whether it's addressing aggressively their metabolic risk factors, etc. 

Melanie Avalon: I really, really love that analogy you made with the burnt bricks. It actually reminded me of another analogy that I often hear that I'm dying to hear your larger thoughts on, especially since it is one of the four pathways. With the lipid dysregulation, what are your thoughts on cholesterol and its role? The analogy I was thinking of it similar, a lot of people in the low carb world will say that cholesterol is like-- it's not the root cause and then it's not necessarily a bad thing depending on the context. What are your thoughts on lipid dysregulation and HDL, LDL, triglycerides, and how that relates to Alzheimer’s? 

Dr. Dean Sherzai: We go by the cumulative data. The cumulative data, be it from the vascular side, from the inflammatory side, from the amyloid side, from the genetic side, which is APOE4, from all of these things show high lipid levels are bad. Now, there's a differential between what lipids and whether it's low density, or it's cholesterol, all of that stuff. That's not as important. People are making it important because humanity's need for confirmation bias is just so massive that it can actually drive entire industries and entire movements. I say that people love hearing good news about their bad habits. I was growing up in Pittsburgh. I used to eat fat and meat and all these things seven times a day and if somebody would have said anything, I would have just-- A young man, an athlete being told not to eat fat, that's just crazy. What are you telling me? If I would have found somebody, anybody who would have martialed or led the path that said, bacon is medicine, that would have been my hero. The data is all otherwise. The data, whether it's from the Harvard study, whether it's from the Columbia University, or the California Teachers study, which we studied in, or the Adventist Health Study, where we are actually working in, whether it's from any of the studies shows that lipids and fats are not good for you, especially, saturated fats. 

Dr. Ayesha Sherzai: Right, Yeah, all fats are not bad. It's the specific type of fat that has been associated with poor outcomes. The good thing is we have tremendous amount of data that points to one direction and of course, there is some data that shows the contrary. That's how science is. You have one side showing you one thing and a number of studies pointing to the other directions. As a consensus and when guidelines are created, you essentially rely more on the amount of data that points to the greater amount of data that chose to point towards one direction. As far as fats and lipids are concerned over and over, whether it's cardiovascular outcomes or for Alzheimer's disease, it's been seen that saturated fats, consumption of saturated fats, have been associated with higher risk of Alzheimer's disease. We can go into some of the details too whether it's from the aging project in Rush University where Martha Clare Morris, she was the lead author of the papers that define the mind diet, whether it's Dr. Paul [unintelligible [00:29:06] from the Adventist Health Study, whether it's the Northern California study that looked at close to 10,000 people over many years, higher saturated fat consumption and higher LDL levels, especially during midlife, seems to increase the risk for Alzheimer's disease and also vascular damage in the brain. 

Melanie Avalon: To clarify for listeners, because saturated fats don't directly enter the brain, right?  

Dr. Ayesha Sherzai: Right.  

Dr. Dean Sherzai: No, they don't.  

Melanie Avalon: So, what's happening there with the fat and the brain? 

Dr. Dean Sherzai: One of the things that we're seeing is, we see patients two days a week, so thousands and thousands of patients, anybody who has memory disorder, one thing that's not diagnosed or is not recorded, because there's no ICD-10 code for it, is white matter disease. What we're seeing universally and ubiquitously in people who have high cholesterol is white matter disease. White matter disease is vascular damage to those connections between neurons. The most vascular organ in the body is the brain. If you ever look at the one of those pictures where they've denuded the brain of all the other tissue, and they've just left the vascular component, one wonders where's the room for anything else, because it looks like billions and billions of vessels in the brain.  

Now, those vessels get smaller and smaller as they get to the cellular level, we've talked about capillaries and yes, they're separated through the blood-brain barrier. What lipids do and saturated fat does, it actually damages the endothelial lining, it damages those vasculature. So, you actually get significant damage, even shorter strokes, what do we call-- and it’s actually not the name, but we call millions of micro strokes. But literally, it's that. It's damaged to the cellular level via through inflammation or through damage of the endothelial lining or it's through little microvascular damages, which is millions of little strokes. 

Dr. Ayesha Sherzai: You hear that the brain is made out of fat, so it needs fats to survive, that's true. The brain is made up of fat, but it doesn't require saturated fats or cholesterol, because first, they don't pass through the blood-brain barrier like we discussed right now. Second, the kind of fat that's in the brain is structural fat. This is the fat that makes up the lining of the extensions of the neurons, brain cells. It makes the walls and the membranes of these different cells, and they don't need to be replaced on a daily basis. The brain itself can actually sustain the infrastructure of the brain by creating the necessary raw materials and the cholesterol that it requires can be produced in the body. The only type of fat that the brain needs on a regular basis are omega-3 fatty acids. We need to consume those every single day. The rest we don't need. 

Dr. Dean Sherzai: In fact, the one thing that has changed our mind, well, in the last year per se, because we just did two comprehensive reviews, which are painful forms of research. You have to collect all the data on a subject matter and then make sure that you're staying true to the subject matter was omega-3 in two papers. One was omega-3 in the developing brain, which is children, even pre-birth and the first few years, and omega-3 and the aging brain. What we found is that we need a lot more omega-3 than we thought. So, we're not against the fact that if somebody wants to take omega-3 supplements, that's fine. If they're not, they should be very, very, very cognizant of their source of omega-3. That's one type of fat that we definitely, definitely need. 

Melanie Avalon: For those who aren't vegan like, “Are you okay with krill oil and things like that, or is it better to get the algae form? 

Dr. Dean Sherzai: We go by data. We ourselves are vegan for multiple reasons. But their data against fish is not there. Fish seems to be healthy. Most of the data shows that fish is healthy. We have to stick by the data so that people trust what we're saying. We can't become dogmatic one direction or-- Yeah, if they want to get fish, that's fine, fish oil, if they want to get krill oil. We think that we worry and this is extrapolation. Now, extrapolation is weaker data. Just to show that the transparency of what we're trying to say. There's data-driven material where multiple scientists come together in consensus, that's the strongest form. Actually, people keep talking about randomized clinical trial, because that's become the popular thing of the day, because some podcasts talked about randomized trial. Reality is, no true population-based data can come out of randomized clinical trials. You don't have the funds to run it long enough to give you a population-based data. It makes some much sense. You need all of those kinds of data. You need retrospective, you need perspective, you need randomized clinical, and population based. All of those are needed. Consensus takes all of that together, multiple scientists and they give it-- So, that's the strongest. 

What we're doing next, which is I'm going to extrapolate, which means from how much I know and what I worry, I say this, take it for what it is. We worried that if people take fish-based omega-3s, we check for inconsistently. By the way nutraceuticals, they're never check. But we check in consistently for lead, mercury, and PCBs. But we don't check for other 30,000 chemicals that accumulate in animals. We worry about that. That's basically it. So, we avoid it for that reason and others. But to be honest, the data is not there against consuming fish as far as health and brain health is concerned. 

Melanie Avalon: The toxicity with the different environmental chemicals and how they accumulate is a huge, huge concern of mine. I had mercury toxicity pretty bad and ever since then, I've been so, so aware of it. 

Dr. Dean Sherzai: Just to belabor that point even more, we've added 30,000 chemicals into the water systems. Yes, plants can get toxic as well, and all this, but as biofiltering organisms or-- 

Dr. Ayesha Sherzai: Concentrators  

Dr. Dean Sherzai: --concentrators which animals and fish are, the bigger the fish, the more chemicals that they will accumulate. For example, an animal like a tuna, which eats multiple smaller animals, they accumulate lots of toxins. A carnivore that's higher in the chain is going to accumulate much more toxins. So, one has to be aware that-- and by the way, none of those toxins we check. None of them.  

Dr. Ayesha Sherzai: Right. Not a standard of care at least. 

Melanie Avalon: I went deep in the rabbit hole trying to find all the research I could find on mercury specifically, but toxicity levels and fish, and the difference between a piece of swordfish, for example, and tilapia, the difference could be the equivalent of having 300 pieces of tilapia and one piece of swordfish. Now, when I see that on the menu at restaurants, I'm like, “Please, please don't order it.” So, while we're in the fat world, what are your thoughts on MCTs for Alzheimer’s?  

Dr. Ayesha Sherzai: Yeah, MCTs are highly fractionated fats. They're processed and they're marketed in a way where it suggests that they can be used as fuel for brain cells. The research that has come to us are from very, very small populations of individuals who have advanced diseases of the brain. But we don't have any evidence on larger, relatively healthy populations to tell us whether that works or not. The idea is these medium chain fatty acids when they're given to the brain, they're going to be used as fuel as opposed to glucose being used as a fuel. It essentially creates an artificial environment for the brain to stop functioning its normal duties and function on a shortcut that was biologically created when human beings were under duress or under stress. For example, in states of starvation, or disease, or immense amount of stress. That may work for a shorter period of time, but we really need to expand on strengthening the normal biological processing and extend their life for long as possible. So, we don't suggest MCT oil right now for people who want to avoid diseases. We actually don't have any evidence of MCT preventing diseases like stroke and Alzheimer's disease and when it comes to advanced stages of the disease, we don't have strong data that actually works. 

Dr. Dean Sherzai: This is a very good point. Thank you, Ayesha. It's critical to know what to base public health on. People can do whatever they want on the individual basis, but public health advice is very, very important to be accurate and based on the latest data. Now, our favorite phrase in our household, we have two teenagers, it's to the best of our knowledge today. To most laypeople, that sounds like that's a weak thought process. "Wait, if you don't have perfect data, then well, how can--" No, everything around us is based on that concept. Even the telephones, the airplanes, to the best of our knowledge, the knowledge moves forward, and we have to adjust with the best knowledge in front of us and that works.  

To the best of our knowledge today, glucose is the best form of energy. Not fast glucose. We're talking about complex carbohydrates. Not simple processed, chemically laden carbohydrates, but complex carbohydrate, it seems to be for the great majority population. I'm not talking about celiac disease population or the 2% that are gluten allergic, but for the general population, that seems to be the beneficial. Whether a ketogenic diet is beneficial, there has never been a long-term study. That's important for me to say. I know that you might have population that might not like this, but long-term data matters, because something that can that is beneficial short term does not necessarily mean it's beneficial long term. 

Dr. Ayesha Sherzai: But that said, we're very, very excited about the research that is going on.  

Dr. Dean Sherzai: Yes.  

Dr. Ayesha Sherzai: We're hoping to learn more about it and just really looking forward for clarification of this incredible opportunity to learn more about dietary patterns.  

Dr. Dean Sherzai: Just again almost to the point of access, we are not against any of this data until the data is validated. 

Melanie Avalon: I love hearing so much and that's one of my favorite things about this show, is bringing on viewpoints from all the different sides, because the thing that scares me more than anything is becoming dogmatic about anything. Actually, my concern, because I do think a lot of times, ketogenic and low carb diets can be very therapeutic for people, but one of my concerns and you touched on it just now, and I don't think we talk about this enough is that, I think people can be too casual with it. What I mean by that is, you were talking about how the difference between making recommendations for an entire population versus the individual. I think people flirt with the ketogenic diet and so they'll take in really high fat macronutrients, but it's like if they're not actually being ketogenic, or if they're having too many carbs, or if they change their mind, and then they just go back to normal eating, then they're in a state of a very high fat diet, which makes me nervous. I feel that the high fat diet, it's very, very context dependent in having the health benefits and so, I think people can get a little bit casual with it.  

Dr. Dean Sherzai: I love the way that you explained that.  

Dr. Ayesha Sherzai: That is beautiful. 

Dr. Dean Sherzai: That is beautiful. You've had many conversations on this. 

Dr. Ayesha Sherzai: I think that's the most important point. I think most of the conversation should pivot around just what you said right now. How do we translate all of this fabulous science that is coming to us from the echo chambers of scientific communities to the population? Are we causing more discomfort, and more misunderstanding, and misguidance by all this conversation about nutrition? Because there's a lot. There's a lot of noise out there. Everybody's probably coming from a place where it exists. Nobody creates things, so maybe some people do, but most of it is there. But how can we contextualize it into populations is where we need to converse. 

Dr. Dean Sherzai: The ketogenic diet came from our field from neurology, but specifically a subpopulation of children with seizure that was intractable.  

Dr. Ayesha Sherzai: Yeah, Lennox-Gastaut syndrome? 

Dr. Dean Sherzai: Lennox-Gastaut syndrome. These poor kids had seizures multiple per day, and even for anti-epileptics willing control it. So, they put them in a shock state, which is ketogenic diet. Now, first of all, that should just put give you a pause. Why would we take a disease state as a model for the rest of the population and what it did for that population is not what we want to do for ourselves? Because it put ourselves in shock state to stop seizures is not what we're trying to achieve. We're trying to get optimal nutrients and energy source to the brain, so that it can optimally operationalize, not become quiet. That was the whole point of it in that context. Yes, it was applied in other populations as well, but not as much. Given that we've deal with it on a regular basis, we recognize how difficult it is to truly attain ketosis and, here's the big part, to truly maintain ketosis for years. In fact, find me one population that has been documented, population I'm saying, to maintain ketosis for long periods of time. So, what we're doing is we're introducing a concept based on that paradigm. Even there was a meta-analysis recently, and if you look at the meta-analysis, the papers that are intimate analysis like three people and five people, none of them longer than six months. So, just because it was called meta-analysis, all of a sudden that took over media. 

Dr. Ayesha Sherzai: Also, I have to say, when they say, it better outcomes, yes, there were some changes in the neuropsychological testing, but it was not a clinically significant outcome. It was essentially just numbers. Does this make people's memory better, do they function better, can they drive again, can they do their laundry again, can they carry on a conversation without forgetting who the other person is in front of them after five minutes? That didn't happen. The clinical significance was not there. That's why when we say we don't have any evidence, we get challenged, "But look at the numbers." Yeah, the numbers might be a little different from baseline. But that did not really change the course of the disease. As a matter of fact, it could actually even harm and there was some evidence to show that people's LDL went up and their metabolic risk factors got worse after they stopped it. 

Melanie Avalon: It's interesting, because I guess the one population, people often use as an example is the Inuit. They have something in their genes that actually makes them not as ketogenic, which is very interesting that they're the one population that would be long term, but they have a genetic adaptation to not be ketogenic as much. 

Dr. Dean Sherzai: Yeah, you're right. But also look at their cardiovascular outcomes that have been recently looked at. 

Dr. Ayesha Sherzai: Yeah, when they did autopsies on them, most of them had clogged arteries. They had atherosclerotic diseases of the heart and their vasculature.  

Dr. Dean Sherzai: Which as it happens, nobody ever talks about it. 

Melanie Avalon: Do you know if they had that historically before processed foods became introduced? I feel like they have had a dietary shift. 

Dr. Dean Sherzai: We don't know that. We don't know that, but reality is, we can't use the data where it serves our purpose and not use the data where it doesn't serve our purpose. We don't know that. If we're going to say that they benefited, yet the cardiovascular system was not benefited, then that stands for all the data that came before and after. 

Melanie Avalon: On the flip side, we just talked a lot about low carb and ketogenic diets, but you do talk a lot about the very problematic role of sugar on the flip side. Something I learned that blew my mind was that the insulin degrading enzyme also degrades amyloid, and so when it's being used on insulin, I'm guessing we can't quite degrade as much of the tau or amyloid? 

Dr. Ayesha Sherzai: Yeah, absolutely. It's almost saturating the system, where you're in damage control mode and not in the thrive mode. That's exactly what happens. I think one of the things that we think is the main problem of people vilifying carbohydrates is because it's been looked at as a- 

Dr. Dean Sherzai: Monosyllabic. 

Dr. Ayesha Sherzai: -yeah, monosyllabic thing. When you say carbohydrates, my goodness, there are different types of carbohydrates. Fiber is a carbohydrate. So, nuance is necessary in language. All carbs are not bad. Complex carbohydrates are the most important source of fuel for brain cells and we need these complex carbohydrates in a specific amount at a specific time of the day for our brain cells to use them as nutrients, as fuel. Like you said, when we saturate our system with refined carbohydrates or sugar, let's just call it sugar, what happens is your body goes into a frenzy, your insulin receptors, your insulin, regulating hormones and enzymes, they go into frenzy, and your body completely forgets how to use it as fuel. That's when the inflammatory processes start and the damage starts.  

Melanie Avalon: For listeners, I will definitely just plug that you've got to get The 30-Day Alzheimer's Solution, because it has an epic list of recipes and everything that you could ever want for implementing the dietary choices and it's a really, really beautiful book. 

Dr. Ayesha Sherzai: Thank you. We put a cake on the cover because we wanted to shock people to show them that, “Yeah, you can have a cake for and have a healthy brain, healthy food, and healthy eating doesn't have to be deprivation."  

Melanie Avalon: No, I love that. I love that so much. Another huge question. You talk a lot in your books about the role of activities in the brain, memories, complex activities. There's a lot of discussion about brain games and stuff like that. What role does actually using our brain play in our brain health? 

Dr. Dean Sherzai: Oh, wow, I would say, we were always asked about nutrition. We both have master's in nutrition and we Ayesha is also a cook, and when we live around this concept-- 

Dr. Ayesha Sherzai: We eat a lot of food.  

Dr. Dean Sherzai: We eat a lot of food. [laughs] that’s right. But cognitive activity is the most important thing. 

Dr. Ayesha Sherzai: Absolutely. 

Dr. Dean Sherzai: This incredible brain, we're talking about a brain that functions constantly at a rate that a supercomputer today is-- There no supercomputers that are functioning at the rate that our brain is. Why? It's not just to find a mate. For some of us, it was complicated. Ayesha would attest to that, but it's not just to find a mate. It's not just to run away from the tiger. It's data. It's a data-hungry organ. We talked about good stress and bad stress. Bad stress is the stress that's not driven by your purpose, that doesn't have clear directions, that doesn't have clear victories or successes, and that creates this long-term state of angst and anxiety, and what we call autonomic overdrive, which destroys the whole body.  

Now, here's the good stress and your brain needs good stress almost as much or more than oxygen, and blood, and nutrients, because it needs to be challenged. In order to maintain those connections, it needs to be challenged, it needs to be pushed. There are 87 billion neurons. Each of them can make a couple of connections or as many as 30,000 connections. Although earlier we said that, yeah, there's not as much neurogenesis, but what there is throughout life, even people in their 90s, is more connections. You can make connections and those connections are not small matter. There are a huge matter. They're protection. Imagine if each neuron of the 87 billion make 30,000 connections instead of 5, 6, 10 connections. That's protection. That's brain growth. That's knowledge. So, neuroplasticity is that those connections and how you get those connections. Just like blueberries, I always attack Sudoku. 

There's nothing intrinsically wrong with Sudoku, but we did a meta-analysis, which was published on PubMed in 2018 major journal. I’m very proud of that meta-analysis and looked at cognitive activity and mild cognitive impairment or avoiding Alzheimer's. What we found was three major things. One was purpose, two was complexity, three was challenge. Activities that have purpose, which means they are driven by your passions or your wants. They're complex, which means multiple domains of your brain are challenged. Challenge means you're continually pushing yourself to the next level. What does that look like? Well, that looks like learning a new musical instrument. That looks like learning a new song with that musical instrument. That means that looks like learning a new dance. That looks like running a company that you would have always wanted to. That looks like volunteering. That looks like playing cards with friends, complex cards. That looks like drawing. That looks like building. That looks like things that you would have loved. That looks like classes that you always wanted to take, and not histology like we had to take in medical school. But it looks like that. Why? Let's take one of those and I've used this analogy a lot, but I love it.  

Ayesha is an amazing singer on top of everything else. I play guitar badly for 30 years but I love it. The cacophony I create comes from this. When you're playing a new musical instrument like a guitar, you're reading the notes, that's your left parietal lobe. You're processing it visually, your occipital lobe. You're processing it cognitively, your frontal lobe. You're being creative, it's your parietal lobe. You're emotionally invested in the music, that's your limbic system. You're dexterous with your fingers and coordination, that's your cerebellum and your motor cortex. That's no Sudoku. That's your entire brain being marshalled to the battlefield. That grows your brain more than anything else and you don't have to pay anybody a penny. You don't have to spend money on an app. Find your purpose and put yourself all into that purpose. 

Melanie Avalon: I love that. That's a fun prescription to get from a doctor. So, enjoying an activity and mental stimulation activity versus not so like a kid being forced to memorize something for school. Do you know if that plays any factor, whether or not you're enjoying it?  

Dr. Ayesha Sherzai: Yeah, I think you're pointing to good stress and bad stress. Any activity that brings joy and is connected to your purpose and something that you look forward to doing again, that is good stress. That's the stress you want. For example, Melanie, you've been doing this podcast and I'm pretty sure, preparing for it, and having all these amazing people on your show. That's quite a lot of work but it's your good stress. Bad stress is one that has no purpose, that has no outcome, that has no end to it, and that actually causes a lot of damage to the brain. It not only causes damage physically because of all the cortisol, and the adrenaline, and the harmful chemicals that are produced, but it also becomes a chronic issue. Vasculature, your blood vessels get involved in it, and that's why when people are under chronic, uncontrolled stress, they're at a higher risk of developing Alzheimer's, and they literally have smaller brains. Their brain atrophy starts very early in life.  

Dr. Dean Sherzai: The one thing though, with the kids. If you let a kid, I can imagine myself when I was young, what would I like to do is basically play it. How can you introduce math, and science, or business, or how can you introduce these things that are not just running around outside because you need to do those? Where we go wrong in our educational system, like is based on success. Like is based on tension and release. Meaning, there should be a little bit of tension where the brain is pushed, where the person is pushed but then there's room for success. What we do in our educational system is either we make it too hard, because we have to fit 35 people. So, a group of people for them, it's too hard, so they actually feel the tension too much. It creates anxiety that is not relieved, and they start disliking it because the brain puts a title on those things. Big titles. I like it, I don't like it. Because it's not at the right phase. Or if it's too easy, it bores people. So, what should be done, for kids especially, is giving them tasks be at math, physics, and all of those topics can be fun. But it should be right at the edge of where they are, where they're feeling the tension, but then the doorway of success and creativity opens up and that pushes people towards that learning and curiosity. What we do is we keep closing those doors by making it inappropriate for where they are. Sorry, a little bit of tangent on human behavior but I love that concept.  

Melanie Avalon: No, no, I love that. It reminds me of-- I was studying recently conversations and what makes you likely to engage and it's like if it's too familiar, then you're just bored and you don't engage, but if it's too alienating, and you don't understand, then you check out, because you can't engage. So, it requires that perfect balance of being slightly novel, but familiar enough to be safe. Very, very fascinating. What about multitasking? It seems to me that's really working your brain, but you talk about the studies on multitasking and them not being favorable for the brain. 

Dr. Ayesha Sherzai: Our brain is not made for multitasking. And by definition, multitasking, doing multiple things at the same time, people may feel that they're good multitaskers. I hear a lot of my patients and clients say, “Oh, I'm really good at it. I can do multiple things at the same time.” The usual response, and I think we've said this many times, is there's no such thing is multitasking. There's only doing multiple things badly. It essentially highlights the underestimation of this fascinating organ that we have. We can do multiple things at the same time but we have to keep it siloed. We have to keep it on track. You basically take on an activity or a project, you end it at a particular time, and then you start another one. Don't assume that you're going to be able to do all of them at the same time, because your brain doesn't have the capacity to attend to each and every detail of the tasks. When we multitask, and when we consider this as a normal thing, it affects our focus and attention. One of the things that is critically important for us to have brilliant minds is to continuously focus and attend to a task at hand. 

Dr. Dean Sherzai: Beautiful, and it's critical to also note that we keep talking about dopamine, dopamine, dopamine, and people use dopamine as, okay, it's a motivation. So, what does that mean? Dopamine has to do with success of survival. That's why there are two main systems involved in dopamine. One is movement, gets you moving away from threat and if you succeed, the dopamine is released. The other is behavior, emotion. But they're both connected. But they both are related to success. So, multitasking means doing multiple things. A lot of times, even if you accomplish one of the tasks, the others are left, unfinished, so it leaves the sense of disarray. A sense of dissonance and discomfort. That is actually a sympathetic state, which affects the body significantly. I will explain that part in a second, but you can do multiple things.  

Richard Branson has 300 companies, but he's one of the happiest persons because I've heard him talk about this, is he isolates each behavior to its endpoint and those don't have to be long endpoints. Break activities into small chunks of achievement and make sure that when you achieve them, you check it off, either visually or cognitively, "I got it done." That sense of accomplishment creates the true motivation. We don't believe in the word 'motivation,' except in this concept, which is when you accomplish something, your brain feels good, the dopamine is released, it pushes you to the next activity. So, you can do multiple things, but break them down into those chunks of achievement, and that creates a pattern, that creates positive habits, that creates direction. Where we go wrong is when we create these undefined, amorphous behaviors, and multiple of them, and put ourselves into it, and yeah, maybe we may be able to accomplish one of them, but the rest of them have left this very weird and awkward feeling in us, which damages us physically and emotionally and as far as accomplishment is concerned, they demotivate us long term. So, that's basically it. 

Melanie Avalon: That really, really resonates with me. Probably the thing that keeps me most happy and sane in my life is my planner and it's very, very detailed, because everything is on it all the time and then things get checked off. But if they're not done, they're still there. So, I know they're still on the list, so I don't have to worry about them not being done or me forgetting them. I don't understand not having a planner. 

Dr. Ayesha Sherzai: Just to add to that, I'm going to make a grand statement here. But all of us multitask in a way all day long. We actually have micro multitasking, even when we're conversing with someone. I get patients coming in and say, "I walk into a room and I don't know why I'm there," or "When I'm having a conversation, I lose my train of thought because I don't remember where the conversation was going or where it started. Am I having Alzheimer's disease?" When you look at their lifestyle, they've been essentially trained not to focus at a task in hand because there's so many other things going on in their mind. The energy is completely shifted, they become very demotivated and what happens is, even if it's a simple conversation, they can't even be creative. Forget about creativity, they're actually struggling to keep their thoughts on a track to finish that conversation. The good news is you can train your brain to be more focused, more attentive, and to shut down a thought in your head and completely focus on one action at a time.  

Dr. Dean Sherzai: What we're very proud of the second book, The 30-Day Alzheimer's Solution, is the fact that yes, it has 75 amazing, easy, healthy, tasty recipes that has behavioral aspects as far as sleep and stress management, all of that. But at its core, it's a habit creation machine and that's important. Because if all we did was just throw some recipes at people or what food is good or what food is bad or how to exercise, it just creates more tension. These 30 days, we were very uncomfortable with the name because a lot of times when people use that, it's a gimmick. We didn't mean that in 30 days you're going to reverse Alzheimer's. Definitely not going to reverse Alzheimer's or you going to avoid disease. But in 30 days, you're going to learn the foundations of how to create healthy habits that can last a lifetime. That habit creation is about what we just talked about right now. How to manage the dopamine, so you are in control as opposed to it. 

Melanie Avalon: I love that so much. Again, for listeners, I'll put links in the show notes we talked about so much. I'll put links to the studies, to the books, everything, so you can check out there. They'll also be a complete transcript because I know we dove deep into a lot of things. But thank you so much, Dr. Dean, Dr. Ayesha, this has been amazing. Your book just really, really opened my mind, no pun intended, so much that I had no idea about and I learned so much. You're doing incredible, amazing things for so many people. On that note, actually, the last question I ask every single guest on this show and it's just because I realize more and more each day how important mindset is. What is something that you're grateful for? 

Dr. Dean Sherzai: I'm grateful for having this brain. Not because my brain is any special, just the ability to sense the world, the ability to sense others suffering, the ability to sense the fact that this brain can give me that capacity to do things for others and help others. That is the greatest gift in the universe. So, I'm thankful that I've been given this tool not just to serve myself, but the people around me, and the people around us, and this planet. 

Dr. Ayesha Sherzai: I was going to say the same. We've lived together in the same environment.  

Melanie Avalon: 18 years. [laughs]  

Dr. Ayesha Sherzai: But I'm really grateful for having the opportunity to hopefully make a difference towards a better world for all of us. We have two children, Alex and Sophie. They're 16 and 14. I see how they think and how they perceive the world around them and that makes me so happy and hopeful for our future. I'm really grateful to be able to connect with individuals outside of our immediate family and friends like yourself to talk about important things like brain health, mental health, and health in general, not just for human beings but for the planet. 

Melanie Avalon: Oh, that is so wonderful and again, I cannot thank you both enough. I, so, thoroughly enjoyed the books. This conversation was incredible. Thank you for being open to discussing everything, and all the nuances, and I just I can't wait to air this episode for my audience. Is there any other links that you'd like to put out there for people to best follow your work? 

Dr. Ayesha Sherzai: We love connecting with everyone. we are sherzaimd.com, and @sherzaimd on Instagram, Facebook, and Twitter.  

Melanie Avalon: Perfect. Well, I'll put a link to that in the show notes. So, thank you both enjoy the rest of your day.  

Dr. Dean and Ayesha: Thank you so much.  

Melanie Avalon: Thank you, bye.