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The Joe Rogan ExperienceThe Joe Rogan Experience

Joe Rogan Experience #1870 - Max Lugavere

Max Lugavere is a wellness journalist, filmmaker, author, and host of the "The Genius Life" podcast. His new book, "The Genius Kitchen," is available now.  https://www.maxlugavere.com/

Max LugavereguestJoe Roganhost
Jun 27, 20242h 45mWatch on YouTube ↗

EVERY SPOKEN WORD

  1. 0:00 – 3:01

    Max’s origin story: his mom’s Lewy body dementia and “diagnose and adios” medicine

    1. ML

      (drumming) Joe Rogan podcast. Check it out. The Joe Rogan Experience. Train by day, Joe Rogan podcast by night. All day. (instrumental music) What's up, Max? How are you? What up? Thanks for having me. Nice to meet you. Same. I've enjoyed your content online, so it's exciting to meet you in person. Thank you. I'm glad to hear that. So, you were telling me, before we got rolling, I said save it, let's just talk about it. What, uh, this Alzheimer's- Yes. ... thing that you're doing? What are you doing? Yeah, so I've been deeply immersed in the, in the Alzheimer's dementia prevention world for the past almost, almost decade at this point. Um, I'm not a ... just to lay it out up front, I'm not a medical doctor. I didn't take the academic route. Um, I started college sort of on a, on a pre-med track, but what ended up happening was, uh, I ended up going into journalism straight out of college, and I ended up working for a TV network in the US, um, that was backed by Al Gore back in the day. And so I, I got to hone my storytelling chops there, but I'd always been really passionate about health, nutrition, medicine, things like that. But in 2011, my, my mother started to display the earliest symptoms of what would ultimately be diagnosed as a form of dementia called Lewy body dementia, which is like a rare- Mm-hmm. ... form of dementia. One in f- Robin Williams had that. Yeah. Yeah. Terrible condition. It's, uh, it's described as, as feeling like having, like you have both Alzheimer's disease and Parkinson's disease at the same time, and certainly that's what I, what I observed in, in my mom. And so, when she started to display those symptoms, um, it had taken me and my family completely off guard. I, I had no prior family history of any kind of neurodegenerative condition. Um, my mom certainly wasn't old at the time. She was 58. She was still, you know, a spirited, youthful woman in, in middle age. Um, she had all the pigment in her hair. And, um, for me, I was in between jobs and I, I really had the opportunity ... I was grateful to have had the opportunity to, to, to go with her to different doctor's appointments. And I grew up in New York City, so we had access to, you know, cathedrals, to medical, um, advice and, and, uh, and, and examination. And in every instance, we were met with what I've come to call diagnose and adios. Basically, a physician would run a battery of esoteric tests on my mom, scribble down a few notes on a prescription pad, and, and send us on our way. But we had to ultimately take a trip to the Cleveland Clinic in Ohio, which is known for taking on really complex medical cases. They build a team around the patient. And it was there that for the first time my mom was diagnosed with a neurodegenerative condition. She was prescribed drugs for both Alzheimer's disease and Parkinson's disease. It wasn't, um, until a few years later that she actually received the Lewy body dementia diagnosis. But at that point, um, I started to dive into the research, because I had been trained as a journalist, which, you know, you're not trained as rigorously as a, as a PhD scientist, but you're kind of taught similar- similarly to investigate things, to maintain skepticism, to, you know, ask questions. And I started to look into the literature and, and just generally get a sense of what it was that my mom had been diagnosed with, what, what this, what this,

  2. 3:01 – 3:31

    Dementia starts decades early: turning fear into prevention mindset

    1. ML

      you know, what this entailed. And I realized that in most cases, dementia begins in the brain decades before the first symptom. 10, 20, 30 years even, um, by some estimates. And so for me, this became something really important, uh, to explore as a potentially preventable condition, because I realized for the first time that I had a risk factor, that my mom, you know, was my risk factor essentially. I didn't ... I hadn't even yet looked into my genes at that point. But, um, but so I, uh, I started looking

  3. 3:31 – 6:56

    Building 'Little Empty Boxes': documentary work, research access, and clinical collaboration

    1. ML

      into it and I came across all of these like fascinating insights which, which we can talk about, but I decided at that point, um, that I ... to, to sort of do what I could to help push the, you know, move the needle with this condition, um, that I would use my skills which at the time were, uh, filmmaking, 'cause I had just come off, you know, I was like producing content for TV and I was on camera. I was a communicator as well. And so I decided to do a documentary, um, on the topic of dementia prevention. The first ever, uh, documentary on dementia as a potentially preventable condition. We've all seen dementia documentaries on, you know, HBO and networks like that, and they're always, they always push this, this very like doom and gloom, um, mentality about the condition, which I, which I understand. It is a very difficult condition. It's America's most feared condition after all. Um, and this is a condition that, you know, 90% of what we know about Alzheimer's disease in particular, which is just one form of dementia, has been discovered only in the past 15 years. So it's a very rapidly evolving field of science. But I felt like if we know that this is a condition that begins in the brain decades before the presentation of symptoms, then to me what that is, that's a very empowering insight. That means that we have agency to change our cognitive destiny. So I started shooting with my mom, which was very hard to do, um, because, you know, I mean, my, the person who I love most in the world I was watching, um, decline right in front of the camera. But also, um, I decided to exploit my media credentials at the time to then talk to researchers and scientists around the world. Um, and I was doing my own research in the primary literature as well. But I decided to, um, to yeah, to go to these labs and clinics where they're really ushering in dementia as a potentially preventable condition, and I actually signed myself up to become a, a, a, a s- a study subject in one actually, at Weill Cornell in New York. Right. And, um, and I actually became, ultimately I became, um, a collaborator with the, uh, principal investigator there, who's become my mentor over the years, Richard Isaacson, um, and I got to, uh, co-author a paper in a clinician's textbook, uh, on the clinical practice of, of dementia prevention, 'cause, you know, uh, uh, after all this time, I've learned so much about, um, about the condition, the etiology and, and so forth. Uh, but this documentary, I'm super excited for it. It's, um, it's called Little Empty Boxes, and we have a trailer up at littleemptyboxes.com. Why Little Empty Boxes? Well, it's a, it's a nod to something that my mom says in the film, which is actually something that d- ... You know, w-... my mom's condition, it seemed like her cognition had just severely downshifted, almost, almost overnight. Um, and so my mom never, my mom never, like, forgot who I was or anything like that. The, the presentation of Lewy body dementia is different from Alzheimer's disease. And once you've seen one case of dementia, just generally speaking, you've seen one case of dementia. Every, every dementia is, is different. But in my mom's case, it led to her often losing her train of thought soon after, uh, beginning to express an idea. Um, and she would often say things that just, you know, didn't, didn't make logical sense. So it's sort of a nod to what, um, to something that she, you know, that she says in the film. But, uh, I'm super excited because we, we inked a partnership with a, uh, a wonderful foundation called the Alz- Alzheimer's Foundation of America. And, um, and, um, yeah, I'm just super excited to, uh ...

  4. 6:56 – 13:59

    Genetics vs environment: ApoE4, modifiable risk, and the “Western lifestyle trigger”

    1. JR

      Is dementia purely genetic or is it caused by environmental factors or any other things that people consume?

    2. ML

      Great question. Um, so though dementia ... Though Alzheimer's disease was coined in 1906 by a physician named Alois Alzheimer, the brain has long been thought of to sit in sort of the ivory tower of the brain, guarded from what happens down below by what's called the blood-brain barrier. But we now know that the brain is influenced by everything that happens down below. And the, the dogma, especially with regard to Alzheimer's disease fundraising over the past couple of decades, has really been that this is the on- this is a condition that you, you can't treat, prevent, or slow. But we now have really solid data to say that we actually, that it is a, it is a potentially preventable condition. So when it comes to, uh, our risk for developing Alzheimer's disease and other forms of dementia, there are basically two categories of risk. You have your non-modifiable risk factors, of which there are three. So you've got your age, your genes, and your gender. So your age: age is still the number one risk factor for developing Alzheimer's disease, right? You can't change your age, yet. You, um, you have your gender. If you're a woman, your risk is double that as compared to a male's. And you have your genes. Now, genes is something that we can actually talk about, because though you can't change your genes, making them therefore a non-modifiable risk factor, you can change y- the expression of your genes, how your genes express themselves moment to moment. So for example, if you live in the United States and you carry a copy or two of what's called the ApoE4 allele ... So it's basically a polymorph- polymorphism, meaning it's not a mutation. It's actually a very common g- gene variant. About one in four people carry the ApoE4 allele. In the United States, that increases your risk anywhere between two and four, fourteen-fold, depending on whether you carry one or two copies.

    3. JR

      I think that's also the same genetic expression that makes you have CTE.

    4. ML

      CTE, yeah.

    5. JR

      Yeah.

    6. ML

      It, it, it, it makes everything more ... It makes your brain more vulnerable, in general, to insult, whether that is from TBI, uh, exposure to pollutants, exposure to unhealthy ways of eating.

    7. JR

      Do we know why it does that?

    8. ML

      Well, it's interesting. Yeah, so the ApoE4 allele is thought to be the ancestral version. So it's the first version. All, all non-human primates are ApoE4. So they carry the ApoE4 allele, not just one copy but two copies, and yet they don't develop Alzheimer's disease. When you look to people, we've evolved, uh, these different isoforms of, um, the ApoE gene. So we have ApoE2, 3, and 4. And just to reiterate, ApoE4 is the ancestral allele. So cultures that have, um, longer exposure to modern agriculture, actually, there's lower frequency of the ApoE4 allele. The thinking is that, that agriculture, right, like when we became domesticated, when we started basing our diets around grains, when we became more sedentary, less, uh, generalized in terms of our, um, cognitive, the, the, the daily cognitive tasks that our ancestors would have undertaken, that it's selected against the ApoE4 allele. So it's possible that that allele, which again is very common, one in four people carry it, carry it, is sort of the canary in the coal mine for the, for the Western way of life. That if you adopt a Western way of life and you eat ... You know, today, 60% of calories that adults consume come from ultra-processed junk foods, right? We're more sedentary than ever before in human history. We've got more stress. We're exposed to more environmental pollutants. That that is what dramatically, is what pulls the trigger, right? Because genes load the gun. It's our diets and our lifestyles that pull the trigger. But if you were to take somebody with that same genotype, right, and move them to a less industrial, a less industrialized part of the world, like say, Ibadan, Nigeria, where the frequency of the ApoE4 allele is just as common, it has no assoc- it has little to no association with Alzheimer's disease. So just to put that another way, what that suggests is if you're genetically at risk for developing Alzheimer's disease in the United States, you might simply move to Ibadan, Nigeria or another less industrialized part of the world and see that risk abolished.

    9. JR

      So with this consumption of, uh, processed foods that p- is responsible for a large percentage of the calories that people consume today, is the human body adapting to that? Is that why this ApoE4 is less prevalent than it is in other cultures?

    10. ML

      You know, it's possible, although with, with age being the primary risk factor, it's unlikely that, um, that that has put significant selection pressure. Um, so I'm not, I'm not act- I'm not sure. But we do know, you know, there are, I think, gene studies where they've looked at, um, expression of, uh, genes that produce enzymes that break down amylase, right, like starch and things like that, and those are increasing, I think, over time. It's a little, little out of my wheelhouse, but, um...... but generally, I mean, yeah, the standard American diet is completely aberrant from the diet, you know, that our ancestors consumed, the diet that, that, really, we attribute to the development of the human brain. 60% of the calories that we consume today come from ultra-processed, packaged convenience, convenience foods. Um, it's a massive problem. I mean, it's driving obesity, it's driving Type 2 diabetes. If you have Type 2 diabetes... So, going back to Alzheimer's disease and, and this, this gene expression. So, the APOE e4 allele is, you know, you have it, but it's not necessarily destiny. And 90% of Alzheimer's cases... I'm sorry, more. Nine, like 99% of Alzheimer's cases are attributable to some interplay between our genes and our environment. There's a very small proportion of patients with Alzheimer's disease that have a gene mutation that is a deterministic gene, um, and this is called the early-onset familial Alzheimer's gene, and that gene basically guarantees that you're gonna have Alzheimer's disease. But that makes up only 1 to 2% of cases. The vast majority of people who develop Alzheimer's disease, um, it's the interplay between their genes and their, and their environment.

    11. JR

      So, excluding environmental factors like pollutants and plastics and all sorts of other things that affect people's bodies, what, what are the other things that a person can do to make sure that they, uh, at least are preventing the, the possibility of this happening?

    12. ML

      Yeah.

    13. JR

      Like, so, if you're saying that, like, if the, if the symptoms take, if it takes decades to, to exhibit symptoms, what are they seeing when they say that the, the people exhibit signs or exhibit some sort of a, a, a future of dementia? Like, how, how can you see that? What are you seeing?

  5. 13:59 – 18:50

    Early brain changes: glucose hypometabolism, insulin resistance, and what testing can (and can’t) show

    1. ML

      Yeah, I mean, so there, there, you can't necessarily look inside the brain. Um, I mean, you can. There are, uh, studies that look at what's called brain glucose metabolism. So, something that you see in Alzheimer's disease is a redu- a reduced ability of the brain to generate energy from glucose. This is called glucose hypometabolism. This is a very, uh, this is a, a defining feature, actually, of Alzheimer's disease. And I say Alzheimer's disease... Again, my mom didn't have Alzheimer's disease, but it's the most common form of dementia, and so all the research on it really looks at j- m- mostly Alzheimer's disease. And then you get s- sort of, like, all-caused dementia in there, but, like, these, these more niche variants, like Lewy body, like frontotemporal, there's very little research on them. So, when I say, sometimes I use Alzheimer's disease and, and dementia interchangeably, but, um, but with Alzheimer's disease, one of the primary features is called glucose hypometabolism. So, the brain's inability to create, uh, energy from glucose.

    2. JR

      So, you see that decades before you see symptoms of dementia?

    3. ML

      Yeah, especially with people who are genetically at risk. About 10 p- a 10% reduction in the ability to generate energy with, out of glucose, which is the primary energy substrate for the brain under fed conditions.

    4. JR

      S- so if people see this if they, uh, uh, get a test and they ru- they find out that they have this APOE e4-

    5. ML

      Yeah.

    6. JR

      ... and then they, um, get their glucose che- how are they checking that, their, their ability to process glucose?

    7. ML

      Yeah. I mean, they do what are called FTG pet tests scans. Um, so they'll just look to see glucose uptake in the brain. But, um-

    8. JR

      Where does one get... Like, if someone is saying, "Oh, my God, I have dementia in my family-"

    9. ML

      Yeah.

    10. JR

      ... and they're listening to this. What can, how can I find out?" What do they do?

    11. ML

      You know, it's, that's not a test that you can easily get. Um, they'll use it for, uh, study purposes, like research purposes, but it's not a test being used clinically. Um, the, the, what correlates very closely with reduced glucose metabolism in the brain is your degree of insulin, uh, resistance in the body, or sensitivity. So, if you are insulin sensitive, you've talked many times on the podcast in the past about metabolic health, insulin sensitivity versus resistance. The sort of classic condition that we see here in the US characterized by insulin resistance is Type 2 diabetes. But what the studies have shown is that insulin resistance correlates very closely with reduced glucose metabolism in the brain. So, what you really wanna do to keep your brain healthy is to make sure that you're as insulin sensitive as possible. That's one thing that you can do that, um, you know you're checking off that box, 'cause when it comes to... So, we talked about the, the... And let me know if I should, like, you know, kind of double-click on any one of these, because, you know, I know we're covering a lot. But when it comes to the, the other, uh, risk factors, the, what are called the modifiable risk factors, you have 12 of them, and one of them is diabetes. So, insulin resistance, obviously the hallmark of Type 2 diabetes. We know that insulin resistance is strongly correlated to reduced glucose, um, utilization in the brain. Um, obesity is another modifiable risk factor. Studies show that as your waistline expands, your brain shrinks. Total brain volume is actually inversely-

    12. JR

      That explains Bert Kreischer.

    13. ML

      Yeah. (laughs)

    14. JR

      Call Bert. He needs to know about this.

    15. ML

      Um, so yeah, obesity is no bueno. It's not good. You know, I mean, there's like this push online now of like, the healthy-

    16. JR

      Body positivity.

    17. ML

      Body positivity, yeah. I think it's big problem.

    18. JR

      So foolish.

    19. ML

      Yeah.

    20. JR

      I just, I, I can't imagine being so sensitive to people's feelings that you ignore a very clear warning sign that they're doing something that's insanely unhealthy and preventable, and it's something that should be broadcast to everybody. Everybody should know this is, this is a real factor in a host of different b- uh, problems that are gonna happen with your body.

    21. ML

      100%. I mean, you can be more or less healthy at a given size, right? But to be not obese is healthier than being obese.

    22. JR

      100%.

    23. ML

      Yeah.

    24. JR

      Yeah.

    25. ML

      And by the year 2030, one in two Americans are gonna be not just overweight, but-... obese.

    26. JR

      I thought it was already there.

    27. ML

      We're close, we're 40%, but we're getting there. It's insane.

    28. JR

      (laughs) Yeah. It's, and it's clearly connected to our diet.

    29. ML

      Yeah.

    30. JR

      And, you know, that's one of the things that I have enjoyed, uh, is a lot of your posts on diet and food, uh, but, n- we, we should, we'll get to that. But, let's, before we get into that, t- when you talk about preventative measures that someone can take, other than decreasing your waistline, losing weight, what do, what are the other factors? Does exercise have any factor on, uh, dementia?

  6. 18:50 – 23:23

    Lifestyle prevention toolkit: exercise, blood pressure control, and resistance vs cardio

    1. ML

      Yeah. Exercise is medicine when it comes to the brain. So, and we can tackle this from a number of different angles. But, when you exercise, you're literally pushing fresh blood up to the brain, and blood carries oxygen, nutrients, antioxidants, things like that. Um, when you exercise, you are increasing the expression of a protein called brain-derived neurotrophic factor, or BDNF, which is sort of considered to be like a Miracle-Gro protein for the brain. Uh, you're increasing blood flow, you're increasing the expression of BDNF. You're changing the, the neuro-chemistry of the brain, essentially, with a workout. I mean, I'm a, I'm a different person when I leave the gym than I was walking into it. So you can subjectively, you can feel that, that it's doing something to your brain.

    2. JR

      Yeah.

    3. ML

      You're reducing inflammation, you're reducing blood pressure, you're normalizing healthy blood pressure. This is something that is, uh, this is, I mean, crucially important, but one of the seminal, uh, trials that I use in my argument, which is now, you know, finally being accepted by, you know, the, the, the medical establishment. But, um, the SPRINT MIND trial found that for people who were aggressively treated for their high blood pressure with pharmacologic drugs, but, um, but, you know, this ties into exercise because exercise is, uh, just as effective as blood pressure lowering medication, meta-analyses show. But, for these people who were put on aggressive blood pressure-normalizing therapy, they reduced their, um, the risk of developing mild cognitive impairment. And mild cognitive impairment is sort of a prodrome, it's, it's considered like pre-dementia. You'll often develop mild cognitive impairment before you're diagnosed with that.

    4. JR

      That's also Bert Kreischer.

    5. ML

      (laughs)

    6. JR

      Send him a message.

    7. ML

      (laughs)

    8. JR

      This is, this one's for him.

    9. ML

      Warning sign.

    10. JR

      This one's for you, Bert.

    11. ML

      (laughs) So, yeah. So, I mean, so exercise is like, it, it helps to normalize bl- blood pressure, it reduces insul- insulin sensitivity. It helps to, you know, the hormonal milieu, we talked about insulin resistance. Uh, physical exercise, right? Particularly resistance training, which is so important for people to do. It is one of the best ways of fostering insulin sensitivity.

    12. JR

      Resistance training above cardio?

    13. ML

      Well, car- they're both beneficial. They're both be- And actually, I, um, I like to remind myself this because I dislike doing cardio. Like, I don't like running on a treadmill. I love lifting weights, I've been doing that my whole life pretty much. But cardio is super important because we, we have a ton of evidence on cardio as it pertains to BDN- BDNF, which is this brain-derived neurotrophic factor. And we know this because it's very easy to get a mouse to run on a treadmill and then to sacrifice it and see what's going on in the brain. It's a lot harder to get a mouse to do squats and bench presses.

    14. JR

      Mm.

    15. ML

      You know? So from a, from like the basic scie- science standpoint, we have a lot of evidence on specifically what cardio does for the brain, right? But resistance training we know, in terms of bolstering whole body resilience, robustness, uh, y- we know that your muscles are a very important glucose disposal sink, right? So, I mean, we live in a time where your average American consumes 300 grams of carbohydrates every single day, right? Our bodies don't have, uh, a, a, a way to store carbohydrates beyond what, you know, the storage capacity of our muscles and our liver tissue, right? It's not like fat. You can store 3,000 calories of, of fat in a single pound of fat tissue, right? But, you know, your muscles, your liver combine only about f- four, 500 grams of, of glucose, you know, in a, in a given day. Or it's, or at a, at a time, rather. And so, um, so yeah, r- resistance training, you're building, you're, you're building up your musculature which is gonna allow you to continue to exercise and be mobile, which we know is really important for the brain. Um, for glucose disposal it's crucially important. So, I think, I think both are key. You can obviously tweak your resistance training regimen to have a more sort of cardio aspect to it, right?

    16. JR

      Mm-hmm.

    17. ML

      Like shortening the time between sets. But I do think that there's value in doing, in doing both, you know. Um, but yeah, exercise, it's just, uh, at this point, like, I think it was, uh, two or three years ago that the American Academ- Academy of Neurology finally made exercise a, uh, something that physicians could prescribe to treat somebody who's presenting with subjective cognitive, cognitive impairment in the, you know, as a, as a prophylactic so that they won't go on to develop mild cognitive impairment. So, it's really important.

    18. JR

      Well, that's very progressive of them.

    19. ML

      Yeah.

    20. JR

      I'm glad they're doing that now.

    21. ML

      Yeah. I mean, there's a lot of, um... And I, and I've seen this personally like in, in science. Like, I'm a, I'm a huge fan of science.I, my work relies on it. And, and the last thing that I would ever wanna do is sort of undermine confidence in science. But there's science and then there's the science.

    22. JR

      Right.

  7. 23:23 – 37:22

    Alzheimer’s research scandal: amyloid hypothesis, fabricated data, and FDA approval controversy

    1. ML

      You know? And, um, w- especially in the field of Alzheimer's disease, there was this huge revelation recently that the past 16 years of, um, Alzheimer's research, in many ways, was built on fraud.

    2. JR

      Yeah, I read that. That w- is one of the things that I wanted to talk to you about, because it's so crazy. Please tell people about this, because it's so insane and it, it's so hard to believe that this could happen in modern medicine. And w- especially with something that affects so many people's Alzheimer's, but please, tell people about this study.

    3. ML

      Yeah. So, basically the prevailing hypothesis as to what causes Alzheimer's disease over the past century, right, has been what's called the amyloid hypothesis. So ever since Alois Alzheimer discovered, or named, uh, Alzheimer's disease in 1906, and looked into the brain of a cadaver and saw these, um, plaques aggregating around neurons, right, in the extracellular space around neurons.... the plaques have come to be sort of the force, the, the, the focus of, um, Alzheimer's research, really. And the idea was that these plaques were the causative force in the, in the condition. Um, much like the plaque on your teeth, right? You see these plaques in the brain of an, of an, of a person with Alzheimer's disease. And so, that's really been the target of drug therapy. And the idea was that un- until we can find a drug that would, uh, reduce the plaque burden, reduce the plaque, get rid of the plaque in the brains of, uh, of, uh, a senior person, right? Somebody who's at risk for developing Alzheimer's disease, that it's a disease that you can't prevent. You can't, there's nothing to do to treat. Um, but the problem was that they could never actually tie the plaque to cognitive decline, right? Like the clinically meaningful symptom, the symptomatology of Alzheimer's disease, that it messes up your cognition, that it makes you, you know, that it makes you forget your loved ones. Ultimately forget who you are, ultimately forgetting how to eat, right? And that, and, and, and nourish yourself. They could never tie those symptoms to, to the plaque, right? Until a paper published in the journal Nature in 2006. So, what happened was this researcher named Sylve- Sylvain Lesne at the University of Minnesota basically was looking into these, the brains of, uh, mice who were bred to overexpress what's called, uh, amyloid precursor protein, which is the precursor to amyloid-beta, which is the protein that makes up sort of the skeleton of these plaques that we see aggregate, right? So, what he do- what he did was he isolated a subtype that he called A-beta*56 and injected it into a, uh, young and healthy mouse or rat mouse, and he saw the, that, that mouse's cognition rapidly declined. So, that was the missing link, right? That he found a subtype of this amyloid-beta protein that serves as the backbone of these plaques, which could never be pinned to the cognitive decline itself, right? The memory loss itself. But he claimed that he found it, and when injected into the, into the brain of, into the body of a healthy mouse, he saw rapid decline in terms of their, of their cognition, right? So, that was the missing link. And so at that point, um, faith in the so-called amyloid hypothesis was starting to wane because they couldn't find effective drugs. Um, Alzheimer's drug trials have a 99.6% fail rate, so worse than for cancer, worse than for any other, any other disease state, really. And, um, and the drugs that are currently FDA, FDA approved on the market, they're biochemical bandaids, they're minimally effective. I mean, they modulate various neurotransmitters, but you know, I've, I've heard it described like, uh, you know, trying, expecting to remove amyloid from the brain, uh, of a person with Alzheimer's disease and to see their cognition come back is sort of like thinking that if you remove all the headstones from a grave, you know, people will come back to life, right? Like, there's widespread neuronal dysfunction and death in the brain of somebody with Alzheimer's disease. And in tandem with that, uh, scanning technology has allowed us to look into the brains of healthy controls. And what we see is that there's amyloid plaque in the brains of healthy controls as well. So, there's no correlation between amyloid burden in the brain and one's cognitive abilities. But nonetheless, when this paper came out in 2006, it renewed fervor, um, in terms of this hypothesis, because he found the subtype of amyloid that could be injected into a young and healthy mouse that would then impair, seriously impair their cognition, right? And so that, that renewed interest in this, in this hypothesis, and it's what ultimately led to the fact that just a couple years ago, two years ago, um, there was a highly controversial drug that was approved by the FDA called Aducanumab or Aduhelm. And this is a drug that effectively reduced plaque burden in the brain. For the first time, they found a drug that could actually reduce plaque burden in the brain, but it didn't lead to any improvement in cognitive symptoms. Nonetheless, it was given the green light against, uh, against tons of opposition that the FDA received. They put together a panel of 11 people, neuroscientists, neurologists, right? Eight of them told the FDA not to approve this drug.

    4. JR

      And what was the reason for that?

    5. ML

      The reason for that was that the drug didn't, didn't move the needle on any clinically meaningful, uh, symptom, right?

    6. JR

      Where there's significant side effects for the drug?

    7. ML

      There were. So, 35% of the people in the trial had significant brain swelling, and half of them had, uh, bleeding associated with that brain swelling-

    8. JR

      Ugh.

    9. ML

      ... because it, these are antibodies. So Aducanumab is an antibody that basically targets, causes your own immune system to target the amyloid plaques, right? And so what that's doing is causing an inflammatory response in the brain, right? So, 35% of the patients in that, in the, in the phase two trials, I believe, had horrible side effects and no clinically meaningful, uh, effect on, um, on their cognition. But nonetheless, because it effectively did reduce the amyloid plaque burden, there was this intense pressure, right? To, uh, to get it green lit because that's like-

    10. JR

      Right.

    11. ML

      ... the amyloid hypothesis is right there, right?

    12. JR

      Uh-huh.

    13. ML

      So, huge problem. One of the big, uh, vocal sort of skeptics about this drug, Aducanumab, is a guy, a Vanderbilt researcher named Matthew Schrag. And so Matthew Schrag was like very vocal, vocally against the approval of this drug, which again, doesn't do anything, right? Like, horrible risk of side effects, no clinically meaningful effect on, on, on s- the, on the symptoms that we want to improve, right? Um, for a patient with Alzheimer's disease. And, um, and so he was vocally critical of that, and then he also was working on some other, some other drug, and he, uh, so, uh, what was revealed basically in the science paper that came out was that he was, um, dabbling in, uh, on a website called PubPeer, which is, um, a site where you can go-It's known for post-publication peer review. So, before a paper gets, uh, accepted for publication, it undergoes this peer review process, right? And so, he found that there were a lot of sort of red flags that were being brought up on this message board, essentially, about this Nature paper. This like seminal Nature paper that was published that found to, it was like the missing link, right? Between like, the amyloid hypothesis and like, the clinically meaningful, meaningful, um, symptoms, meaning memory loss. And he did a bit of like, image sleuthing, which is not generally part of the peer review process, right? And he looked at these, um ... the way data is illustrated in this, in this paper, as it is in- in research generally, it's called a Western blot, which is like a visual representation of, of data, the presence of proteins and so forth. And he found that they were all, for the most part, fabricated. In fact, this A beta star 56 wasn't found by any other team. Hasn't been found by any other team. It, it- it basically came to light that it was essentially faked. The whole thing was faked.

    14. JR

      What was the motivation for this person to fake all this?

    15. ML

      Because the thing, I mean, I think that we, we like to believe that science is this good faith endeavor towards human flourishing, right? But in the industry of science, there are flawed humans, just like there are in every other industry, right?

    16. JR

      Yeah.

    17. ML

      And scientists in general, I see this all the time in nutrition, online on social media, right? Social media is a great like, sort of, they say that sunlight is the best disinfectant. Like social media is a great way to kinda see how this plays out.

    18. JR

      Right.

    19. ML

      Because scientists are notoriously territorial, obstinate. They, you know, their, their-

    20. JR

      Egotistical.

    21. ML

      ... reputations. Egotistical, yeah.

    22. JR

      Yeah.

    23. ML

      Their reputations are everything, right?

    24. JR

      Yeah.

    25. ML

      And, um, I mean, it's just like, I see it, I see it every day. I see it-

    26. JR

      They're humans.

    27. ML

      Yeah, exactly.

    28. JR

      Yeah.

    29. ML

      So, yeah, so there's bad apples, right? Like-

    30. JR

      Yeah.

  8. 37:22 – 43:02

    Beyond amyloid: metabolic framing and ketogenic therapy as symptom support

    1. ML

      a ketogenic diet on myself and other ketogenic therapies, because ketogenic diets, what they do ... So, as I mentioned, in the Alzheimer's brain, the ability to generate energy from glucose is reduced by about 50%, 45, 50%. Its ability to generate energy from ketone bodies is unperturbed. So, the idea is that a ketogenic diet can essentially keep the lights on in the Alzheimer's brain. It's not a cure, but, um, but there has been, uh, research, um, on patients with Alzheimer's disease, mild to moderate Alzheimer's disease, that ketogenic, uh, ketogenic diet intervention can actually improve functional capacity in those patients, which is everything, right?

    2. JR

      Yeah.

    3. ML

      Um, so that's what I would do for myself. Uh, for other people, you know, when my mom, um, was starting to show these symptoms, I, I attempted to put her on some kind of like ketogenic-style diet. But actually, as you, uh ... What's very interesting is that people that develop Alzheimer's disease, they, they start to develop a sweet tooth. And it's thought that that's sort of like the brain crying out for sugar-

    4. JR

      Mm.

    5. ML

      ... essentially, because it's just, it's struggling to generate energy.

    6. JR

      Right.

    7. ML

      You know? And dietary change is difficult for anybody, let alone somebody with dementia, so I can only ... Yeah, I can only speak for myself.

    8. JR

      So, even though this study has been shown to be fraudulent, and even though that medication has shown to have some pretty severe side effects, and even though the amyloid plaque hypothesis has kind of been disproven now as being the cause of it, why are they still prescribing that drug?

    9. ML

      (smacks lips) Yeah. It's, uh ... You know? It's, uh ... (laughs) Because it takes 17 years.

    10. JR

      Right. But once they have access to the fact that that study was flawed, not just-

    11. ML

      Yeah.

    12. JR

      ... flawed, but fraudulent. I mean, that's, it's pretty significant, the impact that that's had.

    13. ML

      They should pull it off the market.

    14. JR

      I mean, think about the num- the, the, sheer numbers of people that have dementia and Alzheimer's and s- these significant, horrific problems, and they're basing the treatment of it on fraud.

    15. ML

      Yeah.

    16. JR

      And the fact that they still do it without, like, having this immediate cease, like what could be, other than generating more revenue ... Other than generating more revenue, like what-

    17. ML

      Yeah.

    18. JR

      ... what else could possibly be the reason for continuing to prescribe that drug other than ignorance?

    19. ML

      Yeah. Well, I think that it's not that this paper came out and suddenly the amyloid hypothesis is, uh, you know, has been debunked or whatever, you know? Like, there, there is still a ton of money invested in this hypothesis, and there are still a lot of researchers who think whether or not this drug is, is the, is the ... You know, this is like version one.

    20. JR

      Right.

    21. ML

      So, there are still many researchers who think that this is like still the target, still the appropriate target.

    22. JR

      But once they realized that the study was fraudulent-

    23. ML

      Yeah.

    24. JR

      ... and that when injected into these mice and it's causes significant de- degeneration that this is not really accurate-

    25. ML

      Yeah.

    26. JR

      ... that this is all fake-

    27. ML

      Yeah. Well, this-

    28. JR

      ... so then they don't have a mechanism.

    29. ML

      Right.

    30. JR

      Right? So, why are they still prescribing a disease to combat the mechanism that's proven to be fraudulent?

  9. 43:02 – 56:08

    Nutrition detour: eggs, cholesterol, and Joe’s backyard chicken saga (and why yolks matter)

    1. JR

      Which is, vegans don't wanna hear that, ever.

    2. ML

      They don't wanna hear that.

    3. JR

      Th- they panic.

    4. ML

      Well, I, yeah, I butt heads with them all the time.

    5. JR

      (laughs) Of course.

    6. ML

      Yeah.

    7. JR

      Well, it's an ideology, you know, unfortunately. It's an ideology based on a really good premise. The premise is you wanna do less, uh, less harm. You wanna be a, a more ethical, moral, kinder person. And I, I respect their motivation. The problem is in practice, both in monocrop agriculture, which is horrific for the environment, and then also in the effects on the human body. If you, i- it's very difficult to do correctly, you know, and we've had conversations before, and unfortunately, you know, there's a lot of documentaries and a lot of people that are propagandizing this ideology. They're doing it like it's a religion, and that's how they treat it. They, they ignore any evidence to the contrary. They, they won't even look at eggs-

    8. ML

      (laughs)

    9. JR

      ... which are really kind of ... I mean, if you have chickens, or if you know someone has chickens, or if you can get eggs from a, a place that has, uh, free range chickens, it's like zero ethical dilemma. It's, they lay eggs every day.

    10. ML

      Yeah.

    11. JR

      They're not going to be chickens. It's just free protein. If you let these chickens roam around and eat grass and bugs and do the stuff they're supposed to do, you have literally one of the most healthy sources of food that's available to the human body. And it's ethically free. Like, if you're a person that's a vegan and you're doing it for moral purposes, but you recognize the fact that you're not getting the appropriate amount of nutrition, get chickens. If you have a backyard, get some chickens. They lay an egg almost every day.

    12. ML

      (laughs)

    13. JR

      And they're better for you than any egg that you're gonna buy in a store from grain-fed chickens.

    14. ML

      100%.

    15. JR

      And you don't have to worry about them ch- being treated horrifically. They just w- I mean, I used to have chickens before the fucking coyotes got them all.

    16. ML

      (laughs)

    17. JR

      But, uh, this was back when I lived in California. It's a long story. But, um, it, it w- wasn't just the coyotes got them all. It was like, the fire burnt the chicken coop down. Our ... We almost lost the house. The fire burnt the chicken coop down. Then we had a smaller chicken coop, and then that one wasn't as robust. I had, like, a real serious one built by a carpenter.

    18. ML

      Wow.

    19. JR

      And then we bought a store-bought one, 'cause we had to get a chicken coop quickly and the coyotes figured out a way to get into it.

    20. ML

      Hmm.

    21. JR

      And it was a fucking bloodbath. It was horrible.

    22. ML

      Damn.

    23. JR

      Nine chickens destroyed overnight.

    24. ML

      Oh my god. Wow.

    25. JR

      Yeah, it was, it was fucking horrific. Um, but those little fucks, they had been-

    26. ML

      (laughs)

    27. JR

      ... targeting my chickens for quite a while.

    28. ML

      Wow.

    29. JR

      But the-

    30. ML

      Good eating.

  10. 56:08 – 1:15:28

    Seed oils vs olive oil: processing, oxidation, aldehydes, omega-6 balance, and buying/storing oils

    1. JR

      I definitely wanted to talk to you about that because-

    2. ML

      Controversial.

    3. JR

      This is, uh ... I've been trying to have this conversation with my family 'cause they'll buy salad dressing and say it's healthy. I'm like, "Do you ever read what's in this shit?" I'm like, "Unless it has olive oil in it, it's probably not good for you." Like these shitty seed oils that they put in these salad dressings, I eat salad with the salad dressing on it, I feel like shit.

    4. ML

      Yeah.

    5. JR

      I feel, like, bloated. I feel gross. Whereas I eat salad and I just put balsamic vinaigrette and olive oil on it, and I feel great. It feels like, okay, my body likes this. And isn't, f- like ... Just consuming, like, vegetables by themselves is not as effective as consuming them with some fat.

    6. ML

      Yeah. You're absolutely right. So I mean, a lot of the compounds that we want in- in veggies are fat-soluble. So I talk a lot about the value of carotenoids. So carotenoids are like plant pigments. They're responsible ... Generally in the produce section you'll see, uh, yellow produce and orange produce, rich in these compounds. And two in particular, um, plant-based carotenoids I've become a big fan of called lutein and zeaxanthin. And they've shown that people, higher consumers of lutein and zeaxanthin have ... They- they seem to be protected against, uh, cognitive decline.

    7. JR

      Vision loss.

    8. ML

      Vision loss, certainly. Yeah.

    9. JR

      Yeah.

    10. ML

      If you look at any eye supplement, they usually will have, um, those two in them because they can help prevent age-related macular degeneration.

    11. JR

      Yeah. Now, um, what are the criticisms, uh, against seed oils, uh, specifically? Like, I- I've seen you speak about grape seed oil, which is a really fascinating one, 'cause it really wasn't something that was in the human diet until y- w- as you were saying, that wine makers realized, "Hey, like, we could ... We're leaving money on the table."

    12. ML

      Yeah. (laughs)

    13. JR

      "Grow all this grape seed, turn this shit into oil."

    14. ML

      Yeah. So again, some industrious, uh, entrepreneur saw that as a byproduct of wine-making, you're losing out on all these grape seeds, right? And grape seeds are rich in oil, like- like all seeds are, right? And so if you can extract the oil and get rid of the noxious, like, aromas and- and flavors, then you've got something that you can sell, right? For- for ... I think it's like a $500 or $600 million a year business, if not more, these days. Um, so grape seed oil, like any of these grain and seed oils like corn oil, uh, canola oil, which comes from the rapeseed plant, soybean oil, they're referred to sometimes within the food industry as RBD oils. Refined, bleached and deodorized oils.

    15. JR

      Blegh.

    16. ML

      Yeah. Um, because they're- they have like these like, again, these harsh bitter flavors, right?

    17. JR

      Mm-hmm.

    18. ML

      Some of them, like, uh, like the rapeseed, contain toxins like erucic acid.

    19. JR

      They might wanna change the name of that seed.

    20. ML

      Yeah, right?

    21. JR

      Doesn't it seem like a rude way ...

    22. ML

      Yeah. (laughs)

    23. JR

      You know, you want a murder fruit? No.

    24. ML

      (laughs)

    25. JR

      You know what I'm saying?

    26. ML

      Yeah.

    27. JR

      Like, why is it rapeseed?

    28. ML

      Exactly.

    29. JR

      Okay. So, um, what do ... What's the negative effect of things like, like ... I would imagine that in the human diet, consuming, uh, an exord- exorbitant amount of this kind of grape seed oil is really not even possible. Like, the ... How many grapes would you have to eat to get ... With the seeds, to get the kind of, uh, the amount that you would get from a tablespoon of, like, grape seed oil?

    30. ML

      Yeah. I mean, humans, we don't even, like, generally ... We would ... We- we're averse to seeds for a reason. I mean, if you've ever tried to chew into a grape seed, it's bitter, right? You spit it out.

  11. 1:15:28 – 1:24:53

    Greens, fiber, and gut resilience: oxalates, ‘plant toxins,’ microbiome adaptation, and carnivore as therapeutic

    1. ML

      Yeah. So, I think that the, the, I think balsamic vinegar is great. I happen to love it. And also, people that eat a salad every day, so this is a really cool research from Rush University. Found that people who eat a big bowl of dark leafy greens every day have brains that perform up to 11 years younger.

    2. JR

      Wow.

    3. ML

      Yeah. So, this could be, like, healthy user bias. Like, n- again, nutrition, even my own, the o- recommendations that I make, like, you know, a lot of ... Healthy user bias confounds many, um, of these kinds of studies in the world of nutrition because we just don't have many long-term randomized, you know-

    4. JR

      Right.

    5. ML

      ... large population, multi-center randomized control trials, right? But the research shows that, that, that regular consumers of dark leafy greens, so I like to say, like, a salad a day, that's what this research found, that, um, they have more youthful brains by up to 11 years. And when you actually look at what dark leafy greens have in them, first of all, they're one of the most nutrient dense foods that we have. I mean, most mo- the most nutrient dense foods that we have access to are gonna be animal products, right? But dark leafy greens are up there because they're so calorie sparse, and they are a good source of folate and vitamin C. And we also know that they're one of the best ways to get those carotenoids, like lutein and zeaxanthin, which is not just associated with, um, better cognitive aging and lower risk for cognitive decline. But, um, in young and healthy college students, they've actually shown that when you give people who are already thought to be at their peak of cognitive prowess supplemental lutein and zeaxanthin, that you see a, a, an improvement by about 25% in visual processing speed.

    6. JR

      Wow.

    7. ML

      Yeah. It was a University of Georgia study.

    8. JR

      25%? That's incredible.

    9. ML

      Yeah. And-

    10. JR

      Now, is there any concern about oxalates?

    11. ML

      I think only if you know that you're sensitive to them. I'm not a-

    12. JR

      How would one find out?

    13. ML

      I think if you have, like, you know, kidney stones, like, in your family, things like that. Like, if you are ... Generally, you would know, you know, I think there are genes that play a role in this, or if you know somebody in your family, or if you yourself have had them before. You know, calcium oxalate is what you wanna be careful with, but I don't think that, like, eating a salad a day is gonna put you at risk.

    14. JR

      Is there any benefit of cooking leafy greens versus eating them raw, or vice versa?

    15. ML

      Certain leafy greens can definitely be made more digestible when, um, when you cook them. Uh, but, but, you know, there's always, like, a give or take when you cook or store vegetables. Some micronutrients become more viole- bioavailable, some become less. So, um, I tend to recommend, uh, you know, sort of a mix, like, a, like a, like, variety, you know? Some cooked, some raw. But in general, with the salad recommendation, you know, with dark leafy greens like arugula, kale, spinach, things like that, I, I don't think that ... Spinach is probably the highest with regard to oxalates. So, you know, if you're sensitive to oxalates, um, you know, you might wanna cut down on your raw spinach consumption.

    16. JR

      I used to drink, uh-

    17. ML

      But-

    18. JR

      ... kale shakes all the time, and, uh, I would mix it with coconut butter and a bunch of other stuff in there and fruit. But then I got concerned about oxalates.

Episode duration: 2:45:22

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