 So, welcome to the Dr. Gundry podcast. Now here's a shocking statistic. A new case of dementia is diagnosed every three seconds. Oops, there goes another case right now. So it's estimated that over 50 million people worldwide are struggling with some form of dementia. A number that's expected to rise to 82 million people by 2030, and quite frankly that's right around the corner. In fact, I bet you know someone who has struggled with dementia themselves, either who has already passed or is currently struggling with dementia. Now it hasn't received much press, but there is something that might be a major breakthrough in our understanding the causes and prevention of dementia. And today I'll be chatting with one of the researchers behind this breakthrough, Dr. Dan Goodenough. Dr. Goodenough is the founder and CEO of Prodrome Sciences and has spent the past 30 years researching the biochemical signs of aging and disease and what can lead and prevent dementia. On today's episode, he and I are going to discuss his exciting new research into the causes of dementia, what your blood can tell you about your risk for dementia and Alzheimer's, and why we might just unlock the secrets of how the brain ages sooner than you think. Dr. Goodenough, welcome to the Dr. Gundry podcast. It's great to have you here. Well, thank you, Dr. Gundry. It's a pleasure to be here with you today. I'm really excited to have you on this show because what you've been researching has been kind of a pet project of mine for the last couple years when I first was introduced to these compounds. But I must say that ever since I learned about plasmalogens, I just can't say enough about how important they are and how little anybody talks about them. So why don't we start, give us a little behind the scenes look. You've been doing this for 30 years. How'd you get to Prodromes Sciences and where are we going? Well, thank you for that introduction. Yeah, the story about plasmalogens is actually really an interesting one on many levels. It's an interesting one in terms of just the medical community, but also how science works from beginning to end. It's a really nice story. It's like a detective story where you're following one clue after another to try to find the culprit in the crime here of dementia. And plasmalogens are one of those interesting molecules where they're fossil lipids, they're part of all the membranes of the body. They're not new. We discovered them about 100 years ago. And we've known about them for a long time and we know about their importance. So children who are born genetic mutations that impair their ability to make plasmalogens have extremely high mortality. Very few of them live with age 10. And depending upon the severity of the plasmalogen deficiency, it affects their lifespan. So we know that it's an obligate molecule for the human body. And we know that things that are born prematurely, some of those infants will have what's called bronchial dysplasia, which is basically driven by low levels of plasmalogens. And so the importance of plasmalogens have been known for a long time. And where they are made have also been known for a long time in the special world now called proxiesome. But we just really kind of ignore them because for most of our life, we make it up to them. And it's not a small amount in your blood. 20% of your entire brain lip involving there's plasmalogens. 35% of your heart, your lung, your kidney, your eye function. So we're not dealing with some very esoteric micro molecule that's just found from someone's super high microscope in the human body. We're dealing with something that's quite obligate to human life. And kind of- Let me stop you right there for a second. And let me go back for a second because some of our listeners will say, well, now wait a minute, what the heck is a phospholipid? And, okay, a plasmalogen is a phospholipid, but that doesn't mean anything to me. So why don't we start there? So the best way to deal with phospholipids is to think about the human body. The human body has a trillion cells that's a lot of little individual three-dimensional spheres. And you can think of a human body that's got a very large, massive apartment building. And every one of the individual apartments are separated from other apartments by the walls in our apartment building. And then we also have- And those are usually the heavy structural walls that separate one apartment from another apartment. But then there's rooms within the apartment, how we compartmentalize, how we do things in the kitchen and bedroom and in the bathroom, and we keep things separate. And your body compartmentalizes its activities that way. And what the body uses to make all these walls are called phospholids. And that's the biological material that basically gives the human body its physical structure. So a phospholipid is like a soap that you use for dish soap. It has a polar head group that likes water, so it uses all the water, and has a non-polar or lipid-like molecule that goes into the oil side. It's like having oil and vinegar, and you can get them blended. And what happens is, phospholipids create what's called a phospholipid bilayer, in that non-polar group of one attaches to the non-polar group of another, and the polar head groups stay on the outside. And so that's how the body creates what's basically a biological wall. And then that is- Those biological walls is how the body compartmentalizes all its activities. And so of course, things have to go in and out of these walls, just like in your house. There's neob, windows, neob, electrical outlets that connect one cell to another cell. And you can imagine, if your walls of your house just started to shrink, all of a sudden your doors wouldn't open properly, or they wouldn't close properly, they'd stay open a little bit, maybe with weak air. And so that's kind of where the physical structure of the human body comes in. And a lot of these phospholipids, all of the building blocks of these phospholipids can get in our diet, like colons, and the ethanol means, and our essential fatty acid that we get from our oils over here. Plasmalogens are unique in that virtually 100% of the plasmalogens in your body, your body must make itself. And that's what gives it a very- It's kind of the most interesting planned also lesson. It's like building a wonderful washing machine and just intentionally putting a weak belt in there, knowing that it'll work for 20 years, but sooner or later that belt's going to fail. And that's kind of the proxies of the human body. So your body has the nice thing about plasmalogens is it requires no dietary requirement. You can make plasmalogens from the simplest fat molecules on the planet. So you don't need omega-3, you don't need omega-6 or omega-9. So your body, plasmalogens are so important to the body that it doesn't require any dietary nutrient. But that is also its Achilles' heel, because since it doesn't require any dietary nutrients, you actually can't get it from your diet. You have to make it. So as we get older, and as the population gets older, we start seeing proxiesome failure from liver damage and strong, and it's very well reproduced in many, many studies. And so our ability to make plasmalogens starts to decrease with time. And of course it doesn't decrease gradually. Some people have great proxiesome function until they're 100 years old. And some people start failing in their 50s and 30s. And so we have those types of discrepancies. And when you talk about science, people like to show these nice, beautiful graphs of how this molecule decreases with age. But that doesn't actually, that's not how it happens for individuals that you meet. Most people will have normal levels for quite some time. Then something will happen, and then it'll drop off. And then they'll have low levels. Then when we average all the people together, it gives a nice, beautiful looking graph on a piece of paper. But that's not really what happens to individuals that you meet. So what happens to make those graphs go down, it's the number of people who become deficient increases. So say when you're 50s, maybe only 5% or 10% people have low levels. Then you're 60, 16, 15 to 20, and then 30%. So people with good normal levels have the same, they have the same low levels in their 90s that they have when they were 30. So they have no change. But the number of people with low levels starts to increase. And that brings the whole average down. And then when geeky scientists like us make graphs, it makes it look like everybody's cosmology levels decrease a little bit every year. And that's really not how it happens. So that's what cosmotons are. And what's really interesting, what gives them their special powers is a special bond called a vinyl ether bond. And that's what gives it its antioxidant capabilities. Like it's massive free radical scavenger in the bottom. But it's also that vinyl ether bond is what gives membrane fusion. So the release of neurotransmitters in the brain is why they're highly correlated to cognitive function. And it affects protein function in the membranes. So it changes the fluidity of your membranes so that the proteins do the important work. So that's the thing. And so in that special bond, that vinyl ether bond, unfortunately, is very sensitive to acids. So since our body has lots of plasma acids, what do you think, if you eat a nice juicy steak or animal products that you should be eating plasma acids? But that vinyl ether bond is sensitive to acids. And so when it hits your stomach acids, which is basically concentrated hydrochloric acid in your stomach, it breaks that bond down. So dietary sources of plasma acids are minimally bioavailable. So that's the fossil-lipid part of the story. Okay, so we make them, if we're lucky enough, we make them all our lives. So what does this have to do with dementia? Because obviously, plasma antigens are needed in our brain. So keep with this detective story. Yeah, so this is where it gets really exciting. So back in the 90s, we had this whole genomics revolution. The whole scientific method was changing. People were starting to say, you know what? If the normal scientific method was, you have a hypothesis, you say, you know what, I wanna test this hypothesis. And I'm gonna design an experiment to prove or disprove my idea. And so you presuppose a question to answer. But in the genomics revolution, when we started sequencing the human genome, people said, well, we don't know what all these genes do. Let's just sequence all of them, right? And let's do large-scale, big-data-type research, measure everything, and then we came called hypothesis creating in that we would generate the data first and then from that data, try to understand what's going on. And that changed the scientific method for the first time in millennia. But that happened for the genetic system. Biochemistry, so my background is a synthetic organic chemist and my PhD is in psychiatric medicine, looking at the biochemical mechanisms of psychiatric disease. So neurochemistry, how neurons and how cellular systems in the brain interact with each other. And so at the biochemical level, we didn't have that kind of technology. We couldn't measure all the small, all your neurotransmitters and all the stuff we get from our environment. And so I had to stop a little bit from my research and become a bit of a toolmaker. So I invented this technology called non-carbated metabolomics, which allowed us to measure thousands and thousands of small molecules in any kind of biological dimension, you know, human blood, for example. And that allowed us for the first time to measure thousands and thousands of things without any knowledge beforehand. So I didn't go looking for plasmalogens. Plasmalogens came looking for me. That's where the story got interesting. So when we did this study on humans with different levels of cognitive impairment, and we measured it using this technology, measured thousands of molecules in the blood, a whole bunch of these molecules that had this very strange molecular formula were decreased in individuals with dementia. And the level of their decrease correlated with the severity of the cognitive impairment. And I didn't even know what these molecules were at the time. I didn't even see these things. And so, literally, I Googled this back in early 2000s and this plasmalogen molecule popped up. Because like I said, we've known about them for a hundred years. And I'm going, what the heck is this going on, right? And so then there's like 30 of them in your blood. There's not just one. And so then that's step one. So okay, so we see this association. Now the question from an association is, is that association causative or is it just an bystander watching an accident on the freeway? And is it part of the accident or is it just a coincidence? And so you go, wow, that's interesting. And so then you have to start studying more research. And then we find out that not only is it decreasing the blood, it's also decreasing the brain of individuals with Alzheimer's. And originally people thought that was because as we get older, we get oxidative stress and it was breaking down these molecules. But what my main contribution was, was that the discovery of this association in the blood, not in the brain, suggesting that actually we're dealing with a liver disease here, more than a brain disease, that low levels of plasma allergens in the blood precede low levels of plasma allergens in the brain. And so that of course required much more research. And so we looked at people, how far before dementia symptoms can we detect this in blood? And on average with seven years, if he pre-secured with seven years before we see cognitive symptoms in humans. And we've done large clinical trials to reproduce this. And then you go one step further and say, well, okay, that's interesting. So mechanistically, how? It's like, so now we've got this true association that's kind of be equal before genotype. We know it's real. We know there's an association. But we have to ask the question. So how is it acting? How is it that this observation is actually creating this phenotype that we can visually see that it's not mysterious that we see cognitive impairment. Cognitive ability is decreasing. And so then we started looking at more detail and that's the correlation with membrane fusion. They're releasing neurotransmitters and how they specifically relate to the colonergic neuron system. So people that have Alzheimer's, anyone who has a family member, he gets familiar with the drugs, the air stuff, that's a pseudo-coloninesterase inhibitor. It's designed to increase the pseudo-colonin. So we know for a fact, and we've known this since the late 70s that the pseudo-colon neurons are the neurons that get impaired. And their impairment is what causes dementia. So the cause of cognitive impairment has been known unambiguously for well over 30, 40 years. But that's not in question. The question comes how and why, what are the reasons for those colonergic neurons to lose their functionality? And then that's where the amyloid hypothesis comes in and so on. But amyloid, again, is a great biomarker, but it's not doing anything. It shouldn't be there. So the observation that increased amyloid levels in the brain, the protein is what Alzheimer's is named for, is clearly shouldn't be there. The question is why is it there? And so we studied the role of membranes and we found that we could, if we increase the level of plasma allergens in the membranes, we reduced amyloid levels. We could actually turn amyloid formation on and off based upon the level of plasma allergens in the brain. And when we looked at human brain samples post-mortem and we corally found that people that had high plasma allergens in their brain had low levels of amyloid in the brain and had high levels of cognitive functioning. So they're in a colonergic neuron system with some better shape. So we have this one step at a time getting closer and closer to, okay, this is not just smoke. This is fire. This is actually causative. And then the next step was to invent molecules that could, since I'm a chemist, I could design biochemical precursors so we could then study, we could selectively increase different plasma allergens. Because the human brain has two main systems. It's your white matter system, which is the insulation part. It protects all your neurons. And so people with multiple sclerosis or autism, it's kind of like a white matter disease, right? And Alzheimer's and Parkinson's, is it gray matter? Is that the actual, that's the copper wire inside the insulation. The insulation, yeah. Right? And so those types are in plasma allergens. When people say, yeah, one omega-3s in my diet, those omega-3s are for the gray matter with a wire on the inside, but your omega-9s, your oleic acid, protects the white matter. So they're very different. So the different plasma allergens in the white matter than in the gray matter. So we could selectively increase different plasma allergen levels and ask the question, what happens if I increase DHA or the long chain omega-3? And when we do that, we improve neurotransmission, we prevent Parkinson's. So if we treat animals with a plasma allergen precursor that has the omega-3 in it, we completely prevent Parkinson's that we can't actually cause neurodegeneration. So animals that have a biochemical reserve of plasma allergens are protected against neurotoxins. And we do the same thing with multiple sclerosis studies. Animals that have a biochemical reserve of omega-9 plasma allergens are protected against demyelination by multiple sclerosis. So now we can get really into that cause and effect because we can say, okay, what happens if I create a situation where an animal has this biochemical reserve? Are they or are they not protected against neurodegeneration? And the answer is unambiguously yes. So we can prove that yes, biochemical reserves of plasma allergens are neuroprotective. And so now that's how the story kind of goes from causation, from an association with disease, to actually being able to mechanistically identify the cause of the mechanisms. So that's pretty exciting. And so we're now at the point where we can look at, and since this is the membrane structure issue, the Alzheimer's is really the canary in the coal mine. So we're seeing this generalized neurodegenerative stress on the human brain. And the question is, what is the weakest link in the brain? What part of the human brain is the most sensitive in the most people with this stress? And that turns out to be dementia. So when you see this plasma allergen reduction in humans, the most probable observation clinically will first be in decreased cognition. That's also associated with increased risks of Parkinson's or stroke as well, that those happen in smaller percentages. So Alzheimer's is kind of that canary in the coal mines. It's, you know, obviously there is some variance in the human population, we're not all the same, but we'll get large numbers of people. The first thing that we observed is we're used to call energy function. So I'm sorry for being a bit wonky there, I hope to explain some of that hemisphere. No, yeah, this is good nerdy, wonky stuff. So let's maybe pull it back to where the rubber meets the road. You mentioned before that we make plasma allergens, we make them all the time. And I think I heard you say that they're primarily made in our liver. And, OK, so what's your hypothesis about why they stop being made in some people and other people who are 100 years old and they're still making them? So I think it's a combination of luck and environment. And probably there's some level of genetics that give you a little bit more resistance to it. So we know the liver toxicity issues with age. If you take a look at liver cancer rates over the last 20 years, it doubles or more. So we have some serious environmental influences occurring in our human populations. That's one thing. So clearly environmental. And people, as they get older, their mobility starts to decrease. So they start walking and exercising less. And your muscles mature, like your proxosomes are stimulated by physical activity, specifically resistance training. So when we see clinical trials where resistance training has such powerful cognitive benefits, that's one of the reasons we see that. It's that if you, resistance training, basically resistance training does takes all your peripheral muscles and kind of turns them into many livers. It wakes them up and they start doing biochemical functions. Because your body is fundamentally lazy. Your body is designed to do at least about a work cost. So if I drop you in the middle of the desert, we want you to be able to walk across the desert, expanding at least a lot of energy. So we're balance, arm swing, our feet walk. So we're going to use our heart. We're going to use our lung for 95% of our activities. And so our biceps and our legs and different things, we kind of only use them intermittent. And so as you get older, we have all of this real estate in the human body to take advantage of. We can wake them up because they really haven't been overused in our lifetime. And so that's one aspect of getting it. So I think mobility, I think our diet, people eat less well as they get older. And so there's a combination of factors, oxidative stress, our balance, our mitochondrial function. So those are the things. So like that's kind of my, I have a personal pet peeve in the aging community in a sense because I don't really believe in aging. We have reduced functionality. Aging is really an association. And so there's many things like this, the human body survives about 60 years in a major of the bulletproof. From age one to 60, you pretty much have to step in front of a bus to die. It's interesting, right? You just, like so the systems are really quite robust and self-regulating. And then we start losing certain functionalities. And so the loss of function is associated with aging. It's not caused by age. And so I think you have these different things, oxidative stress that happen. So that's the kind of thing. So where plasma agents come in, I think people that have healthy lifestyle, they limited drug pharmaceutical use, and then they have a higher odds of being good. But what we have noticed though is that, so in the big university study in Russia, so Russia University in Chicago, their memory and aging and religious order study has been going on for well over 20 years where they tracked people. They had this huge longitudinal data set. And we looked at over 1,000 individuals, 1,200 in some subjects, and we isolated people to top 10%. And it was just a top 10% that had 80% reduced likelihood of dementia over a six-year period. So I think we're almost beginning with a vitamin D situation with plasma agents in that normal levels for most of your life are fine. But just like vitamin D, even though it's theoretically possible to get enough vitamin D if you go out and you get in the sun and you're a construction worker, but for most of us, it's almost impossible for us environmentally to get appropriate vitamin D levels. And I think we're gonna be with the same situation for plasma allergens where roughly only 10% of the population have naturally high protective levels. So the rest of us will be supplemented. Okay, so that brings up two questions. Number one, early on you mentioned that you can certainly measure plasma allergen levels in the blood. Number one, can our listeners walk into their doctor's office or their healthcare provider and say, hi, I'd like my plasma allergen level measured. And of course, they're going to most likely be greeted with a blank stare. Correct. So let's answer that. But then, okay, let's find out about my plasma allergen levels. Oh, and they're low, what can I do about it? So good question. So first of all, yes, plasma allergen testing is available to anyone in the United States around the world, basically. And so if your doctor isn't aware of it, they can get in contact with our laboratory and blood samples can be shipped and your plasma allergen levels can be measured. And we don't measure just your plasma allergen levels, we measure your other fossil levels. If your possible cooling levels, we look at your omega-3, omega-6 ratios, punch with them to your methyl transferase. So we look at more of a holistic approach. Plasma allergen are a critical component of it, but we want to know if your proxisms are working or why your plasma allergen levels are low so we can fix them. So that's number one. Plasma allergen testing is available in a very simple and easy to understand way. So people either program.com or drgoodnow.com, those will be linked up to people that can find that. And then in the supplement, being able to restore plasma allergens, that's been another big area of mine scientifically to understand that. So in our animal studies, we need around 10 milligrams per kilogram is roughly the dose, maybe with the best long-term. Like I mentioned, plasma allergen is in the blood. So average human has about a gallon of blood in them, okay? It's quite a bit of blood, right? And the concentration of plasma allergens is roughly about the total amount of plasma allergens in your blood supply, maybe about a gram, okay? And in your men, all your men, remember your blood is just a, you know, a circulatory system and all your members will have like a hundred times higher. So we're dealing with a significant amount of plasma allergens. And so 10 milligrams per kilogram is like half a gram to a gram is what you need for a therapeutic dose. So important is that, you know, you can't be driving a big semi truck on the freeway and filling it up with a thin bowl of gas, right? So you need to put enough gas in the tank to affect the plasma allergen levels. So the supplementation has to be sufficient enough that a dose that can actually effectively raise plasma allergens in the blood. And so for that, you're gonna need about 400, over 400 milligrams of plasma allergens per day. And so, and that's, I mean, to get that properly in a proper, pure plasma allergen bio available form, that's where my expertise in chemistry and design work comes in. And that's what we've done over the last several years. So we have a really nice, 100% natural, bio-identical plasma allergen precursor. Same concept is held over for Parkinson's. So in order to bypass this stomach digestion issue, okay, we designed a molecule that is two steps up in the biochemical pathway. Because it's the very last step they deliver makes that makes it unavailable in your diet. So we make a molecule that's just, it's a human molecule. It's your natural biochemical, it's your media. It's just two steps up. So then you can eat it, it gets absorbed and actually goes, not just to your liver, but it goes into all the cells in your body, into your brain and everything. So we can directly supplement every cell of body. So that's kind of where you're at. And the nice thing we're testing is that you don't have to take anyone's word for it, right? Like even if you start feeling the physiological effects, which many people do very quickly, when you get retested, it's not black magic. If you can want, here's your blood levels before and here's your blood levels after and you can target the level that you wanna stay at, leave it there and then go on and live the rest of your life knowing that you have a reserve capacity of plasmalogens. So you talk about biochemical reserve. So can you literally build up a reserve of plasmalogens? Yeah, that's exciting part. And so this is really, you know, this is the stuck on stupid part of my scientific career, right? We as scientists, we get so focused on the negative. So I do all these clinical trials. I invented this cool technology that can measure thousands of molecules, right? A bunch of patents in this space. Then we study cancers and neurogenetic diseases and we focus on the disease, okay? What's wrong with the disease? Here's someone with a disease and everything is disease, disease, disease, disease focus, you know? Probably 30 different diseases I've studied and developed biochemical markers for those diseases and biochemical programs, which means how the body changes before the disease occurs. If you just don't walk down the street, it hit by lightning and we got the next morning with stage four colon cancer. But that doesn't happen, right? There's something happens beforehand that sets you up for that. And that's true, measure that. But what I was missing over the 30 years of research was the other half of that colon, is that, yeah, I'm using normal people or healthy people as my other score of the football game, right? That, you know, versus the losing side, which is the disease side. And I'm focusing on what's causing the disease side to be disease. And I was missing the most obvious, what's good about the winning side? Like, why are these people not getting diseases? And that's where the biochemical reserve concept comes in. So this concept of saying, let's look for disease, stop a disease, that only gets you back to zero, right? That only gets me back to baseline. And so we can now move from baseline to biochemical reserve to protective levels and to levels of, and the real fun part of this is how far can we push human longevity and vitality? No one's really thought about it in a biochemical reserve capacity perspective. And say, you know what, we have these systems, we can project them on their downward trend, just move them upward to a biochemical reserve capacity. It's why we take vitamin D, for instance. So a biochemical reserve isn't a new thing. You know, people don't take vitamin C to prevent scurvy anymore, right? Like, you don't take your vitamin D because you don't want to get rickets. Like, no one's getting those diseases. So all of these vitamins, if you take NSD with cysteine or if you take any kind of other supplements for maintaining glutathione or your NAD program. So all of those concepts or biochemical reserve concepts is saying, you know what? I don't want to wait to become deficient. I want to make sure I have sufficient levels now and I don't need to wait for a negative symptom to come in and fix the problem. I already know enough. I don't need to wait for my car engine to run out of oil or gas before I fill it up. I have enough knowledge beforehand. So that's the concept of biochemical reserve. And can we do that in a systematic scientific way? And more importantly, can we do it in a distributable way? This is the UPS FedEx problem, is how do you deliver that type of medicine to large groups of people? Just you mentioned, Alzheimer's. You know, you're talking 30% of the population here. And people don't realize that most people don't calculate in the survival bias in that equation. So when you talk 30% of 90-year-olds that have Alzheimer's disease or dementia, that's 30% of the healthiest of us who actually made it to 90. That doesn't calculate all the people who had dementia before them. So the cumulative incidence rate of a 95-year-old is about 80%. So if you make it to age 95, okay, you've already been without dementia. You're only in that 20% of the population that didn't get dementia. So we're not dealing with the disease. In fact, the people who don't get dementia are the minority, cumulatively. And so that's, I think, what we're kind of exciting about. I think dementia is gonna be one of those diseases of humans that really allow us to think of medicine in a different way. And think of prevention in a different way. And optimization in a different way. And hopefully we can start eliminating age bias where people have to get older, they don't kind of put up with getting older anymore. So I think we've got a good population for that as well. So a couple of things I think I'm hearing you say, number one, depending on the supplement, that supplementation doesn't necessarily make expensive urine. Correct. Okay. And I certainly thought that early in my career, and I certainly don't think that now because I can measure the effects of supplements in people like you can and you can document what happens. The second thing is, okay, so I need plasmalogens and you say it's pretty hard to eat them because my stomach acid is gonna do it. But there are tons of phospholipids. You mentioned choline and many of my colleagues in neurology like Dr. Bredesen and Dr. Perlmutter certainly think there ought to be a lot of choline in our diet. Maybe we should be eating egg yolks right and left. And my colleagues in cardiology go, oh my gosh, choline is the worst thing that you can eat because your gut bacteria are gonna make TMAO out of it which is one of the most lethal compounds for your blood vessels. So you gotta stay away from phospholipids because bacteria eat them and make horrible stuff. So what say you, can help us out here? Well, phospholipids are critical. Choline is absolutely critical. It's one of the most undiagnosed or underdiagnosed deficiencies. Virtually all liver cancers, pancreatic cancer, liver diseases are associated with phospholipidolcone deficiencies. So I'll be presenting a bunch of work of a large over a thousand person study in Chiba Prefecture, Japan on pancreatic and colon cancer in two weeks in Japan. And phospholipidolcone deficiencies are a major association with those cancers. And the level of choline in your blood correlates with your tumor improvement in pancreatic cancer, for example. Choline is absolutely critically important. And it's important because we used to consider choline a non-essential nutrient because technically your body can make it. It makes it from ethanol. But the energy it requires to make it is quite demanding. And so it's a major driver of blood homocysteine levels. So I'm a big, big believer in choline. Now you can argue which is the best bioavailable source whether you get the citric choline or albic, glycerophosphoryl choline or dietary choline. And those are really good questions and arguments because they are metabolized differently. When you take egg yolks, for instance, those molecules get metabolized by the upper pancreatic lysate in your upper GI. So you get lysophosphoryl choline. And phosphoryl choline is another really critical molecule because it's what your liver uses to make LDL cholesterol. If you can't get cholesterol circulation and IB, phosphoethylene therapy has been so amazing results in cardiovascular disease for reduction in energy for our plaques, improvement of cholesterol, transport mechanisms. So yeah, phosphoethylene is absolutely something you don't want to be deficient in. And creatinine, creatine is another one. So your metal transfer system is something that we, and well, everyone knows homocysteine elevation is a bad thing for cardiovascular disease and for Alzheimer's. But most people don't realize why. And the reason why homocysteine is such a good marker is it's usually a biomarker of choline deficiencies because if you are a choline deficient, your body is trying to make a bunch of choline and that happens in the brain as well as in the liver and homocysteine in the background. So long answer to your question, I'm a big believer in choline. You can have an argument over which is the best type of supplement. The pure cholines or the alpha GPCs, those get absorbed without any gut digestion. But the phospholipid versions, they have to go some level of digestion in gut or body sources. All right, good. I'm glad I asked. All right, follow up with that. So how can I, or how can my listeners, what foods can my listeners eat to get their plasmalagen levels up? Is there any way? Not really. The only other sources have negative, like there's substance out there, there's phylogic pool sources out there, phylogical extracts, and usually they have very, very small levels, like a milligram or a few milligrams. And like I mentioned, your blood supply is like a thousand milligrams. So you can just imagine, you're just, you're adding a thin bowl full of plasmalagens into a food pool size pool. And so you're not really making a big impact. The natural sources are like start liverwiles. We'll have some, but they have the negative consequences of the squalene and depending on the saturated side. This is where the scientifically designed side group is important. So we manufacture two types of plasmals in three positions. One is the omega-3 DHA. It's 100% omega-3. And it is pre-packaged with the omega-3 on the balsulipid backbone, on the SN2 position. It goes directly in. It's the only bio-available source of plasmals in three positions that way. And that goes directly into your neuron cells, remembering function. And we have a program, Lea, which is an omega-9 plasmals in three positions. And it has 100% oleic acid. And this is designed specifically for the white matter in the body. And it's very potent anti-inflammatory mechanism, especially in autism and multiple sclerosis. And so that's the unfortunate thing, is that they're in the natural world. That's why these are natural supplements. In case what we basically take as a scary, was naturally found in very small percentages in say a sharp river oil. And we create a pure high-dose molecule that is designed for specific purposes. So people can get confidence that what they're taking, they know what they're taking. And that's kind of a wrap. So it's a, the plasmalogen story is kind of one of those. It's how to get enough of them. So is that, I'm aware, and I don't think our readers or listeners are aware, Japanese study used plasmalogens derived from scallops in treating mild cognitive impairment. And that study was successful. And so there are, were these, are those the sort of plasmalogens that you're talking about? Or is that a totally different animal? Totally different. So that's the fully intact plasmalogen, phospholipid. And that's what gets metabolized by an enzyme called phospholipase A2 in the pancreas, in the upper GI tract. So you get your Liso phospholipid. And the important thing about plasmalogen supplementation is being able to deliver the right plasmalogen for the right purpose. And so yes, if you take plasmalogens from any source, you're going to take enough of them over time they'll have an effect. Okay, absolutely. And so that's great news. The challenge we have to do for the scientific community is do larger studies. We have a trial going on in Santa Monica right now. We just did a trial in Osaka that I'll be talking about. But ultimately, what's nice about the program that we have now is that large numbers of people can take these products. They can measure their own blood. They can measure their own genotypic observations. And collectively, we're going to start generating large amounts of actionable health information. And that's what I'm excited about. So yeah, so plasmalogens can be from other sources. And eventually, we obviously, you know, if you can get them from, you know, enough from another source, it works. But the animal extract process is never 100% accurate. And our system doesn't have any environmental contaminants because we use a 100% vegan process. So we get our omega-3s from an algae source and get our omega-9s from a plant source. And those are sources of the fatty acid, the essential fatty acid for it. And we purify that first from the natural source. And then we connect it to the plasmalogens back home. So what you get is 100% vegan, fully purified product that has no risk of environmental contaminants or plant-based products, or animal-based products. It's not actually extracted from an animal source. So that's the process that we've got. And that's what we've used to test in all of our pre-clinical structure-activity relationships and all of our research and sciences that's behind us. Great. So one last question. My medical practice has a lot of Medicare, a lot of insurance-based practice. And, you know, these supplements are expensive. So why are they so expensive? Obviously, I want you and other people to make a living. But is it the extraction process? Is it the formation process? It's a lot of everything. It's labor, the volume of the manufacturing process. I feel exactly the same way you do. One of my favorite collaborators, Dr. Bennett from the Rush University, says the best preventative has to be as safe as water and just as cheap, okay? And that's kind of where we have to ultimately try to get towards to this ability. So we've been able to systematically improve our manufacturing, improve our volumes. And my number one priority is to get this down into a price point that can be largely distributed because this is something everybody should have access to, period. And I think as we handle this, both from the private paid perspective, so people can just pay for it and we'll bring the cost down as quickly as we can in our manufacturing, but also from the bottom up perspective in the sense that as you run more and more clinical trials and we established scientifically credible evidence of outcomes, but not from a drug perspective, from an actual supplement perspective. And this is what our universities and our government funded research should be doing. They shouldn't be in the business of pharmaceutical drugs. They should be in the business of looking at off patent molecules or natural based medicines, even the aspirin studies and so on and so forth, right? So that people can get bent in the population at a whole. The public should benefit from all of this patented research that's been done. Because once those patents expire, they're supposed to be available for public use. And for public use, that should be our academic resources should be studying these things and making them like, you know, getting aspirin at Walmart, they don't need a prescription for that stuff, right? It's cheap enough. And so as we get better and better at things, these really targeted supplements should be able to get to that point. And then industries really generate sustainable revenues through the service side, okay? Servicing customers, helping them with their blood test, explaining what to do. So you can pay for your time, you can charge for your services, you can charge for this, but have some sort of common interest in the underlying science of these supplements. So I think we'll eventually get there. I think we're seeing this, if you will, democratization of medicine and the people are starting to take things into their own hands. And the power of the people is pretty big. So when you get large vine blocks of individuals, and as we get better information tracking, I think you're gonna start seeing, you know, those shifts occur. Because, you know, we can't ask, and you know, people get a little upset sometimes, but our current medical community is really good at acute care. Like if you get in a car accident, like you're gonna get bit. Because if I get cancer and I need tumor surgical removal, like our ability to handle acute medical needs is really, really good. And our system has worked really well to get there. But it's not really designed for this type of work. It's not really designed for preventative or this biochemical reserve concept. Because, so we're asking, you know, a square peg, if it needs a round hole. And I don't know if it's entirely appropriate for us to be, you know, forcing that on. So I think we need kind of a parallel, I think you're seeing hangers. Like that's why we do my talking right now, right? Because this is, you know, people need this type of information and they need to be able to act on it. Correct. Yeah, that's why I wanted you, you know, I wanted you on the show to highlight an area that I've been fascinated with that, like I say, 99.9% of practicing physicians have never heard of a plasmagogen and wouldn't know what to do with it if they saw it, I think. But once I get it, it's kind of an interesting story because once people hear about it, they get a little annoyed. It's how long have you not known about this thing? Like it's really, it's kind of annoying that, like even myself, like I'm an expert in neurochemistry and biochemical mechanisms. This wasn't even on my radar 20 years ago. And so it should have been. And so I think once you get past that initial shock value and you say, okay, this is, this is something that you should be looking at. And then the interpretation isn't that hard. If people can operate an iPhone, they can understand these blood results. So the blood results, so you're, so how do people find you, find out about you? These, the blood tests and the supplements have to be done through a physician order, if I understand it correctly. That's correct. And so DrGoodNav.com has much more broad-based philosophy in work than we do in cancer, part of asthma disease and neurogeneration. And a part of that is this plasmagistor, which is a really, really important part. And then from there, proteome sciences does all the clinical research part. So any doctor who wants to be part of the program, wants to order supplements, wants to order blood testing, can all be done through the laboratory testing infrastructure there. Any doctor who's on full scripts can get our supplements through the formulary on full scripts. So the accessibility is pretty good. And if any person needs help finding a practitioner to provide them with blood testing resources or supplement resources, we can certainly direct them to individuals for that. And so we'll do everything in our power to help people get the information that they need. All right. Well, thanks for coming on. I think let me conclude with, we both kind of talked over the apoE4 gene. And I think one of the fascinating recent findings about why this gene is so mischievous is, as you know, you have to have phospholipids to carry DHA into the brain. And because apoE4 won't make the proper carriers to get DHA into your brain. I've been, you know. I know it was on my radar to talk to you about too. We get sidetracked with apoE4 story is really an amazing story. Amazing, an interesting story. Because there's three main genotypes, right? There's the E2, E3, and E4s. And these three different genotypes have three very different epidemiological outcomes. Oh yeah. And, but we're preserved. So apoE4, the number thing about before, it's all related to cholesterol regulation and transport. And it's when you're younger, apoE4 is a very protective gene. It creates thicker, stronger membranes. So you're resistant to parasites and bacterial infections more than the right. So that's why it's genetically preserved in our population. It only becomes a problem when you get older, right? And part of this plasmalogen deficiency. So we just published a huge paper on apoE4 showing that apoE4 carriers that have high plasmalogens in their blood have no reduced, no increased risk of Alzheimer's disease or dementia. And we did a big all-cause mortality study and showed that if you corrected for the plasmalogen level in the blood and whether someone had dementia, there was no increased risk of mortality if you had apoE4s in the blood. So we can get this mechanistically down. And so plasmalogens have a big role in cholesterol export, your HDL system, which is the only thing your brain has. So that's where the apoE4 thing comes in. So we have a whole podcast on apoE4. All right, we may have you back with that. But I, well, let's go back with that one. But yeah, so I love, he's a very... I'm sorry I brought it up, but no. I think this is actually really exciting because a huge part of my population are apoE4s. And we've been trying to figure this out. And it's, we work like yours and you're right. Plasmalogens seem to be protective against, you know, this gene's effect. So that's exciting. All right, well, we'll try to have you back, but thanks for coming on the program and good luck with your endeavors. Thank you very much for having me. I hope I've answered some questions and look forward to talking again in the future. All right, very good. Bye. All right, it's time for our audience question. This week's question comes from Juan's Kiko on YouTube. I hope it said that right. Who asks, I wanted to ask if you care at all about phytic acid. Oh, I care so much about phytic acid. No, I'm just being humorous. I have blood iron problems and it seems that phytic acid may be to blame as anti-nutrient impairing iron absorption and other minerals. Flax seeds are on the yes list while they contain a lot of phytic acid. On the other hand, it seems important to include in the diet because of good omega three to six ratio. But flaxseed oil is neither on the yes or in the no list. Do you have an opinion about this oil? Thanks again. Well, so I'm actually for most people a fan of phytic acid. And why is that? Well, it's because that in small amounts and the right amounts, phytic acid can prevent iron absorption. And if you like the iron theory of aging, one of the theories of aging that I like, then higher iron levels associate with basically us rusting faster and lower iron levels within normal ranges. There is some very impressive research correlates with slowing the aging process. So one of the things that we can do in our diet to reduce iron absorption, which most of us get too much of in our diet is to have phytic acid containing foods like for instance, flax seeds. On the other hand, if you are a actively menstruating female quite frankly, you're going to lose a lot of iron every month. And that can be actually very problematic for a number of my patients. So in those cases really you don't want any help in reducing your iron absorption. You actually want to increase your iron absorption. So that's why you'll see flax seed oil is neither good or bad in that I take care of a large number of menstruating females. And so the other thing about flax seed oil, since you brought it up, flax seed oil is a rich source of a short chain omega-3 fat. And I have a lot of vegan patients who believe incorrectly that they can take short chain omega-3 fats from flax seed oil and make long chain omega-3 fats which are DHA, DPA, and EPA. And sadly our enzyme system is horribly designed for that. So you could take all the short chain omega-3 fats and you will really only get about a one, maybe 2% conversion of those short chain fats into long chain fatty acids. Which as we were just talking about today is what your brain has to use. So there are so many better choices for oils to consume than flax seed oil. So I hope that answers your question. So yeah, if you're trying to get your iron up, flax seed oil is way down the list as well as flax seeds. Okay, it's time for the review of the week. This week's review comes from RoboDude69 on iTunes who writes the most logical, educated, and constantly updated health and nutrition advice. I love that Dr. Gundry updates his thinking when he gets new research. Well, thank you RoboDude69. You're right, I am not afraid to tell you that I've learned something new that goes against what I had learned before or I had said before. And thank you for trusting me that when I find something that even contradicts what I said 10 years ago or maybe last year, I'm gonna let you know. And it's based on my reading of the research and often it's based on my patient population and what I've found that they've helped me out with. And one of these days, we'll talk about a recent paper that I presented that upends my whole idea of gluten intolerance. And you'll see more of that in the coming weeks. So great question and thank you for that great comment. So that's all for today. We will see you next week on the Dr. Gundry podcast. Before you go, I just wanted to remind you that you can find the show on iTunes, Google Play, Stitcher, or wherever you get your podcasts because I'm Dr. Gundry and I'm always looking out for you.