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In this episode, you will learn about the role of plasmalogens in cognition and overall health.
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About My Guest
My guest for this episode is Dr. Dayan Goodenowe. Dayan Goodenowe, PhD is a neuroscientist and founder and CEO of Prodrome Sciences. His research into the biochemical mechanisms of disease started in 1990. His curiosity about the biochemistry of life is as insatiable today as it was over 30 years ago. In those more than 30 years, Dr. Goodenowe invented and developed advanced bioinformatic technologies, designed and manufactured novel supplements, and identified biochemical prodromes of numerous diseases including Alzheimer’s disease and dementia, Parkinson’s disease, multiple sclerosis, autism, amyotrophic lateral sclerosis (ALS), schizophrenia, bipolar disorder, depression, and numerous cancers.
- What are prodromes of disease and of health?
- What are plasmalogens?
- Where are plasmalogens high in the body?
- What conditions do low plasmalogens contribute to?
- What factors lead to lower than optimal plasmalogen levels? How can endogenous production be optimized?
- Are plasmalogens addressing root causes of cognitive decline or are they essentially shielding the body from their damaging effects?
- How do plasmalogens impact amyloid precursor protein?
- Can plasmalogens mitigate the potential contribution of ApoE4 to cognitive decline?
- Do plasmalogens have a similar effect in SCI, MCI, dementia, and Alzheimer's?
- How do plasmalogens impact cholinergic neuron function?
- How do other phospholipids such as phosphatidylcholine fit into the plasmalogen conversation?
- What is a healthy cholesterol level?
- From a lipid optiminization perspective, what is an optimal diet?
- Do plasmalogens play a role in traumatic brain injuries?
- What is the ProdromeScan test? Why are specific markers included?
- What are ProdromeNeuro and ProdromeGlia plasmalogen precursors?
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June 23, 2023
Transcript Disclaimer: Transcripts are intended to provide optimized access to information contained in the podcast. They are not a full replacement for the discussion. Timestamps are provided to facilitate finding portions of the conversation. Errors and omissions may be present as the transcript is not created by someone familiar with the topics being discussed. Please Contact Me with any corrections.
[0:00:01] ANNOUNCER: Welcome to BetterHealthGuy Blogcasts, empowering your better health. Now, here's Scott, your BetterHealthGuy.
[0:00:14] ANNOUNCER: The content of this show is for informational purposes only, and is not intended to diagnose, treat, or cure any illness, or medical condition. Nothing in today's discussion is meant to serve as medical advice, or is information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority.
[0:00:34] SCOTT: Hello, everyone. Welcome to episode number 186 of the BetterHealthGuy Blogcasts Series. Today's guest is Dr. Dayan Goodenowe, and the topic of the show is Plasmalogens. Dr. Dayan Goodenowe is a neuroscientist and Founder and CEO of Prodrome Sciences. His research into the biochemical mechanisms of disease started in 1990. His curiosity about the biochemistry of life is as insatiable today as it was over 30 years ago.
In those more than 30 years, Dr. Goodenowe invented and developed advanced bioinformatic technologies, designed and manufactured novel supplements, and identified biochemical prodromes of numerous diseases, including Alzheimer's disease and dementia, Parkinson's disease, multiple sclerosis, autism, Amyotrophic Lateral Sclerosis, schizophrenia, bipolar disorder, depression, and numerous cancers. And now, my interview with Dr. Dayan Goodenowe.
[0:01:37] SCOTT: I recently read Dr. Goodenowe’s book, Breaking Alzheimer’s: A 15 Year Crusade to Expose the Cause and Deliver the Cure. Dr. Goodenowe’s work is cutting edge and provides hope for those concerned about cognitive decline and other neurological disorders. Thank you for being here today, Dr. Goodenowe.
[0:01:54] DR. GOODENOWE: Thank you, Scott. Happy to be here.
[0:01:56] SCOTT: First, what was the personal journey that led you to making neuroscience and ultimately, plasmalogens a major focus of your life's work?
[0:02:06] DR. GOODENOWE: Well, so really, it starts with chemistry and physics and biology from high school, understanding these basic science questions. Then when you look into the – so my first degree is in synthetic chemistry, or organic chemistry. But even from high school, trying to understand how the world around us works. You can look at biology as the interaction of organisms, and you can think of physics as the underlying matrix of reality. We get down into the quantum mechanics of things.
When it comes to the living world that we live in, it's really chemistry. It's the biochemistry. It's the movement of atoms, if you will, and molecules. The human body is this huge biochemical, self-perpetuating miracle, if you will, which is quite – it’s quite awesome. It's really hard for people to really fathom the complexity of what a single human body can achieve.
It goes into the chemistry side of things. Then when you start understanding how that works, then the chemistry of the brain really becomes the next process, because that's really, how do we really transcend from this consciousness to biochemistry, to consciousness? The human brain is really a biochemical simulation of quantum mechanics. We've got such massive computing power that we can actually create that photon wave particle duality, right? Because it really is, it's an interesting thing. How do you choose to eat a chicken salad, versus a burger for lunch? Really, it's really quite – the thing, the simplest things we take for granted is just really not simple, when you really start trying to break it down to its smallest, indivisible parts. That's where it goes.
Then there's a practical aspect of work, right? Understanding technology, understanding, you've got to learn how to skate, or dribble before you can make plays. You have to learn the technology and the tools and all that stuff. That's where my PhD is in Department of Medicine, looking at neurochemistry, looking at the biochemical interactions of the brain related to refractory depression, psychiatric diseases, and that. Then that just one thing leads to another.
Then we go to trying to understand this biochemical miracle we call life. We started in the 9 – I think, the 70s and 80s really was a biochemistry-driven world, even from our medicinal chemistry of the 50s and 60s, where we started discovering drugs and interacted with different receptors in the body. Then we had more biochemistry in the 80s and 90s. Then in the 90s, the genomics revolution really picked off. People started saying, “You know what? We've understood that here's how many genes we have. Here's how introns and exons,” and the whole gene sequencing thing took off, the molecular biology. It changed the way people thought about science.
Science changed from a hypothesis testing model to a hypothesis generating model. Prior to the 90s, you would come up with an idea, you would design an experiment to test that hypothesis, try to make it fail, right? The default is that if you can't make it fail, you have to accept it for the period of time. We've lost that in science. We've lost the fact that science – the job of science is to break things. We're in the business of failure. That's what science is about. It's how do you push things to its failure, until you can't fail it again. We've lost that. It's become more hypothesis proving, versus hypothesis failing.
People get attached to their hypotheses and that's not really a good thing. Anyway, so, and the genomics revolution really came across is that all this technology was being developed; massively parallel signature sequencing, gene chip arrays, and we could take a genome, whether it's a plant genome, a corn plant, or a mouse, or the human body, and we can map all the genes. From those genes, we can predict their expression, the transcripts. From those transcripts, we can predict which proteins are being created and how the genetic differences between individuals can make slight differences in the proteins.
That has a very seductive, logical, God-like feeling where you can understand everything. Because from the gene, every transcript can be found. From the transcript, every protein can be found. That gives you that kind of hierarchical structure. The problem was there wasn't a companion biochemistry technology that could measure metabolism, or biochemistry at the level of scale that we could do genomics from. That's a problem, because the glucose in a plant and glucose in your cat and glucose in you is the same molecule. The biochemistry of our world is not species dependent.
That biochemistry transcends all species and all types of organisms. It's virtually infinite in space. Think about all of the functional – like the clove oils, and you've got extracts of this plant. Then you take a molecule, you take a simple molecule like caffeine and your body metabolizes it. The number of possible biochemical entities is larger than the number of particles in the universe. It's fundamentally infinite in space. There's no way you can create a library of that. It's not philosophically possible to create a library. We need to have technology that we can actually measure it on demand. That's where my build-up of technology and training in advanced mass spectrometry ultimately led to saying, let's use ion cyclotron technology. Can we develop a technology that can be non-targeted, in a sense that it has no a priori hypothesis as to what molecules are present? It just measures everything it sees.
We can derive from that information what those molecules are. This is what the genomics revolution changed in science. It says, “You know what? Let's just collect the data first and then let's compare someone with colon cancer to control, or Alzheimer's and a cognitive, normal person, and let's see what's different. Okay, that's not how we used to do things. We used basically to say, “I think the cholinergic system is impaired.” Then you design an experiment to test that particular thought.
The change was, I'm going to take a group of people with disease A and I'm going to take a group of people with disease B, and I'm just going to look for everything. Then afterwards, I'm going to see what's different. Based upon the differences, I'm going to derive a hypothesis as to why I see these differences. That's a really major multi-hundred-year change in scientific thought, that occurred literally within a few decades. That's where I came in. I know it's a long story.
Now I invented a technology called non-targeted metabolomics. This ion cyclotron uses high-field mass spectrometry and I can measure thousands and thousands of things. It changed your whole view of biochemistry, because we could measure things we could never, ever measure before. We could interpret things we could – then, we started applying that across disease spectrums and that really started understanding – that was the basis of beginning to understand really what health is and the difference between health and disease, and the difference between the deviation from health, or the loss of health, versus the acquisition of a disease.
Medicine has been focused on this. You get a disease. You acquire some negative thing. If I remove that negative thing that you've acquired, you're going to miraculously become better. That is just not true, okay. That's where the actual real data came to be. Anyway, that's a very long answer to your question, which is why we have so many projects going on in so many diverse fields of science.
[0:10:09] SCOTT: You have studied the prodromes, or fingerprints of many different diseases and disease states. In looking at more than 20 of these prodromes, are there commonalities in terms of causes, or in terms of potential solutions? What are the most common health negating and health promoting factors that you've identified and how do we shift from these negative prodromes of disease and death to positive prodromes of vitality and longevity?
[0:10:39] DR. GOODENOWE: Yeah, that's a really good question. Yeah, so as you move up the causation hierarchy, okay, things become simpler and simpler. Because what happens, I say, health is a singularity, right? Your health, my health, everyone's health is exactly the same. There's no difference in health. We deviate in disease. You take a simple disease like type 2 diabetes, for example, right? People have glucose dysregulation. Actually, what they have mostly is reduced fatty acid metabolism, is really what causes type 2 diabetes.
Be that as it may, now we have to predict, okay, we have this deviation from normality. Is this person going to have cardiovascular disease? Are they going to go blind? Are they going to have neuropathy? What's the complication? What's going to be the downstream effect on this person from a relatively simple upstream causation cascade, right? That's where we get stuck in the noise, right? Saying, okay, here's a product for diabetic neuropathy. Here's a product for cardiovascular disease, when these are dealing with symptoms, or complications from an underlying upstream event.
Yes. Certain deviations from normality can have a very diverse clinical spectrum, and that the diversity of the clinical spectrum comes in when you lay on that. Now you put that stressor on a group of people, then that stressor is going to have slightly different effects on different individuals. It's like, someone coming into a lecture theater wielding a 2x4 and yelling like a crazy man. Not everyone's going to respond to that 2x4 wielding crazy man exactly the same. Some are going to run. Some are going to go into the table. Some are going to attack the guy.
One common event can elicit multiple diverse reactions to that event. That creates the complexity of our typical world. Medicine as a general rule has been dealt with from a concept of someone is sick, otherwise you wouldn't be sitting here in front of me and you're asking me, what's wrong with me. It's a symptom-based approach of saying, there's a physical problem of some sort that I need to identify the immediate causation, do an assessment of acute mortality, right? Is this person going to die in the next 30 minutes, next 20 years? And make logical choices.
That is a logical cascade based upon what – and it's been based upon the concept of acute care medicine. It's been extremely successful, so in sense that we don't die of these acute disorders very often anymore, right? Our ability to prevent premature death has been very good. Over the last 100 years, we've corrected – we don't die prematurely of most common things anymore. But that doesn't give us health, okay? What that relies upon is if I – assuming that the person's endogenous normality is there, if I remove that stressor, the person can recover from their own underlying strength, okay?
That model works as long as that person's underlying strength allows them to recover from the removal of the negative influence. If people are weakened, even if you remove the toxin, or you remove the stressor, the person doesn't have the strength to recover from it. This is why we have recurrence of diseases much higher than initial incidence rates, right? People with colon cancer, they get surgical removal, they get a bill of good health. They still will walk out of there with a much higher rate of future colon cancer than someone who never ever had colon cancer in the first place. That makes logical sense when you think about it.
Yeah, so when you look at these cascades, there absolutely is. There's several core components of human cellular health. Peroxisomal function, mitochondrial function, your lipid regulation. That's probably one of the biggest things, like the cholesterol, we have this weird obsession with cholesterol that's not healthy, because – and the data is just not there. It's such a common risk factor, your HDL, and your total cholesterol levels, these things have large distributions of outcomes from cancers, everything else.
This plasmalogen story is a really big hammer, the membrane, we can talk about that in a bit. That are associated with decreased resilience and oxidative stress. The mitochondrial, if you start from the core, the core-core of human viability, the core of human viability is the ability to take advantage of sunlight energy, okay? Humans live on sunlight energy. Plants take carbon dioxide and water, they use the ultraviolet radiation in the sun and captures that, and the chloroplast capture that energy into a hydrocarbon called glucose. Then that glucose gets converted into a bunch of other things. I mean, fatty acids, thousands and thousands of other things. Fundamentally, that's where it all begins. We get energy from the sun is trapped in a chemical bond called glucose.
The human body is a hybrid electric car. We are a hydrocarbon combusting organism that releases that carbon dioxide back to the atmosphere, and we capture the energy from that combustion. The energy from combustion then is used to charge a battery called our electron transport chain. Then we discharge that battery. Just like your electric vehicle, you have a charging process and then you have a discharging process. The charging process is the combustion, creating carbon dioxide. Just the way you heat your house, run your car, it's a release of energy.
Then you charge the battery, which is this proton gradient in our mitochondria, but then we discharge it. How we discharge it is we breathe in oxygen. Oxygen gets converted back to water. It's separate. That's how, so we convert oxygen back to water, which is basically just the discharge of the battery. That's the fundamental concept. We are literally on fire. The human body is burning on fire. It's creating carbon dioxide and water. Think about this. It’s doing this in a distributive battery model. Think of your Tesla car, where every single piece of paint, every single piece of carbon, every single piece of metal, it's in the engine, the fibers that are in the seats of the car, the rubber that's on the tire, every single one of them is the battery, okay. That's the human body.
Every single cell of the human body. We're talking hundreds of trillions, hundreds of trillions of battery cells fully distributed across the entire human body, running 24-7. It's constantly charging and discharging. Okay, it's a constant charge-discharge battery. That is what runs the human body. It’s mind-boggling. It's really hard to even get your head wrapped around the enormity of this thing.
When you come back to this whole process, I’ve talked about plasmalogens and membranes and you get all these things. But really, human life first survives on that mitochondria process. Then everything gets built around it, Peroxisome function. Our membrane structure, our body is built on these apartment complex of cells that have the three-dimensional, like our ability to compartmentalize, right? Just like your house. It compartmentalizes what you do in your kitchen, versus what you do in your bedroom, versus what you're doing in the living room. Things can happen in certain areas without disrupting other areas.
My heart can function without disrupting my brain, for example. That's all done by compartmentalization, and that compartmentalization is all membranes. The biological membranes of the human body, just like the plaster on your walls, but it's all made with biological material. It's made with fossil lipids. Then that quality of that fossil lipid, whether or not that wall can stand without falling down, right? If the composition of your walls change, you'll have differences in your floor and your walls and your ceiling, the different rooms of your home, your outer walls of your house, so we have a different structure to your just separating internal rooms of your house.
You can just think about that. Your human body does that on a huge scale, and it's built that way. When that starts to disrupt, okay, it has other impacts. If you start with the core structural physiological aspects of it, these are all at the chemical level, biochemical. They're tightly regulated. The human body's designed to work, and it works incredibly well. That's where, as you start working down that actual cascade, that's where you start seeing the largest health benefits. That's why low cholesterol, for example, has such a huge distributive death rate, or your membrane structure, like the plasmalogens are when we lose. There's another one with aging.
Oxidative stress is when your mitochondria aren't – that battery is leaking, and that energy now, it's not being converted. It's like, your battery smoking and sparking, and the rest of the body, and we have all these backup mechanisms to compensate for that, and those will work to a certain degree. If those become overwhelmed, then eventually, the body will adapt, and it will try to decide what kind of Sophie’s choices it has to have. Okay, am I going to let this cell die, or am I going to let this cell die? It's going to start making choices. Or what functions am I going to lose? Yeah, I can't do everything anymore. Now, the body has to decide what it's going to maintain and which it's not going to maintain.
Anyways, so that's – I know big philosophical…. As you look yourself down there, so when we're talking about health deviation, this is what becomes so powerful, because we actually know what health is, okay. Once you start studying health, you don't have to study disease. All you have to do is study deviation from health, okay, I don't have to study engine seizures of your car. I just need to study oil usage. Measure the oil, make sure it doesn't get below. I don't have to wait. Here's a deviation from normality. If this is how a car engine is supposed to run, and I can measure the parameters of a properly operating engine, then I just need to keep an eye on that. When one of those factors gets out of whack, you need to fix it.
You don't really need to really say, “Okay, is this lack of oil –” That's a bad example, but what's the ultimate end result of that? Because all these risk factors – take a bracket gene mutation, for example, or you take these things that we talked about with really strong associations. Well, at a pure percentage level, these things are very small. Most people with a bracket mutation will not get breast cancer, okay? You have the risk factor. You can have these stressors, just like a car, if you take a thousand cars and put just a minimum amount of oil in the crankcase, okay, they're not all going to fail right away. Some can run for a long – You'd be surprised. We used to do this in university. We'd do a rally.
We'd take a car and we'd dump all the oil out of the crankcase, and then you would predict how many miles a car would run before it stops. That's what we would use as a raffle for raising money. You'd be surprised at how far a car can run with no oil. The human body is the same way. Just because you've got this deviation from health, it's quite amazing how long we can live in a bad stress environment. That makes it difficult for us, because some of the things that occur to us, we don't see the real negative consequence for years later.
[0:22:58] SCOTT: You say that plasmalogens are the lipids of life. Talk to us about what are plasmalogens, where are they produced in the body, how does the body create them, and where do they then reside in the body, or have their primary biological effects? Is that in the cell membrane? What is their role in supporting optimized health?
[0:23:17] DR. GOODENOWE: Yeah. Plasmalogens, a wonderful story, because it is one of those things that just hits you out of the left field and you go, “How? How is it possible that we have not been looking at this thing?” Plasmalogens are a phospholipid, a membrane. We're talking about those walls of the human body, the body makes walls using what's called a phospholipid bilayer, and it makes it with biological material. It's like soap, basically, in your kitchen. You have a part of the phospholipid molecule likes to be in the oil, and part of it likes to be in water. When you mix them together, the oil components mix together, and the polar separate part, and it creates a biological wall with this fatty – with this oily center, and then this polar charge outside, and then you basically have a wall in water.
That wall material is made, and it has a bunch of phospholipids in it, different types; phosphocholine, ethanolamine. Plasmalogens, fundamentally, are one of those types of lipids. It's not a small amount. We're talking 20%, 30% of your entire phospholipid volume of your brain. 50% of the lipids of your heart that are involved in – we have this huge problem with myocarditis, with the COVID and the vaccines, and the sudden death syndromes that are occurring.
We're not talking about a trace level in the human body. We're talking very, very large amounts in the human body, almost like the level of cholesterol, that level of – high, high levels. It's in every single cell of your body. It's not just, oh, it's just something in your heart, or just something in your brain. That's fundamentally what they are.
The absolute requirement for human life of plasmalogens is best represented by these rare diseases in children that have plasmalogen deficiencies due to genetic mutations. The classic plasmalogen deficiency disease is a disease called Rhizomelic chondrodysplasia punctata, or RCDP. It's about a 1 in 100,000 live birth rate, so it's an ultra-rare disease. Children typically die before age 10. If you're born without plasmalogens, you do not live. You die, okay? Your body will – you will die. It's a horrible situation. They're neurologically challenged. They have dwarfism. They ultimately die of heart failure, or lung failure.
I have a big charity for these children, and so we're having dramatic response rates in them by restoring their plasmalogen levels. Again, this is where you can compensate, or you can even bypass genetic issues, which biochemistry, so biochemistry can bypass virtually almost virtually every genetic risk factor there is out there. That tells you how important plasmalogens are. Why they're important and why they're so strange, it's like cholesterol in a sense, because we don't get very much cholesterol from our diet, okay? Plants, there's no cholesterol in any plants. You get some from animal products, you get some from eggs.
Fundamentally, the human body makes all of its own cholesterol. Okay, 80%, 90%, all your cholesterol comes – and every single cell of your body makes cholesterol. Plasmalogens have a similar situation. We get virtually no plasmalogens from the diet. The only time we get plasmalogens from the diet is when we are being breastfed by our parents, or my mother. The human breast milk has high levels of plasmalogen precursors, and it's designed for the white matter structure. Then of course, that goes away, because we're not breastfed in our fifties. That’s where the natural source of the plasmalogens are.
After that, we make a 100% of them internally for the most part. We usually make quite a bit of them. We're really good at it. It's made in a certain cell called the peroxisome. Your body doesn't even – It's so important to human body that it won't even rely on dietary supply. It says, “No, we got this. We're going to make it ourselves, okay?” Also, it’s a killing field. It means, if you lose your plasmalogen manufacturing capacity at some point in time in your life through either toxicity, or atrophy, then your body comes out of balance. It's expecting a certain amount of plasmalogens, it's not getting that amount. Then deviations from how they occur.
The core component of the plasmalogens, what they actually do the most important, there's about four functions. One that we talk about for Alzheimer's is the synaptic membrane connection between neurons. Again, everything in the human body is done biologically. Interestingly enough, so many things in our regular world work on the same logic. Just like the light switch on your wall, right? You got a switch, you got a wire that's running through the wall. No, there's not a whole bunch of sparks going through your wall, right? You don't want that. Then it connects to your light bulb.
You flip the switch, the electricity goes through the wire, and then at the end of that wire, the coating of the wire is taken off and it either connects, or doesn't connect. That's an electrical connection, right? We do that with physical material, with plastic and copper. Human body, of course, is not made of plastic and copper. It's made of biological material. Everything you think we've done in our regular world, the human body does that with biological molecules and cells. It's a living thing, right?
The copper wire in your wall, in the human body, that copper wire is a living organism. It's living and live and it's being maintained and regenerated every single day of your life. It's alive. When one neuron, or one wire connects to another wire in the human body, there's what's called a synapse. One cell has to then communicate to the next cell. How it does that is by releasing what's called neurotransmitters. These neurotransmitters are released by this fusion. It's like your shower head. You just turn your shower head on and off, on and off. You get this little pulse of water. That's what's happening between cells. Little pulse, pulse, pulse, pulse, pulse.
That ability to open up a cell releases content and then close back down again. It's called membrane fusion. That process requires plasmalogens. In fact, 75% of the ethanolamine phospholipid has to be plasmalogen or more to get that to work. Soon as plasmalogen levels decrease in your brain, that function decreases, and cognition. That's why the plasmalogen levels in the brain are so highly correlated with cognitive function.
It's a really straightforward biophysical process, okay. That's one core component. That's the omega-3, the DHA, the polyunsaturated. That's why fish oils and things have some level of effect, because at least you get an added effect. Plasmalogens are not in fish oil, just to be clear. Fatty acid is in that. That's really core component number one of plasmalogens, is actual synaptic function and your neuromuscular function, okay. So, the connection of your neuron to your muscles is also a synapse. It's called a neuromuscular junction.
Same type of neurotransmitter is in your brain, called acetylcholine. That's why when you see people with Alzheimer's, as they regress, of all the neurological diseases you'll see, Alzheimer's has the most people in wheelchairs, right? Very common, you see this loss of mobility coincides with the loss of cognitive functioning. Mobility and cognition go hand-in-hand in human life and survival. That's one core component.
The second part is actually that the coating on that wire, the plastic coating that's on your wire in the human body is called myelin. You have a cell in the brain called oligodendrocytes, and your cells in your periphery are called Schwann cells, and they make that plastic coating. That plastic coating is called myelin. That's what the Omega-9 plasmalogen does. That's the actual molecule that's in human breast milk. Mother's milk contains the Omega-9 plasmalogen. It's designed specifically for that myelination process.
70%, 80% of the ethanolamine needs is plasmalogen. It's actually the highest concentration of plasmalogens in the entire body. All this connected tissue. Those are two really core things. Then when you talk about this whole membrane composition, so all these proteins that people talk about, these proteins are not just floating around in your body. These proteins are stuck in your membranes. They're like your windows and your vents of your house. They're not just floating in space. They're secured in that membrane. The function of those proteins is dependent upon the composition of the membrane around them. If the membrane composition changes, all of a sudden, the windows are stuck. You can't open them, or whatnot. Plasmalogen is critical for that.
Cholesterol regulation and transport. To reverse cholesterol transport that people talk about, HDL, highly, highly dependent. The foamy macrophage, atherosclerotic plaques, of that whole process where the cholesterol misregulation occurs, and the oxidation of membranes, plasmalogens play a critical, critical role of that. Amyloid formation in the brain, for example. The plasmalogen levels are high determiner of that amyloid plaque. That's number three.
Number four, so there's multiple enzyme protein systems that are affected by plasmalogen changes. Number four is it's really an antioxidant fire hose. It's really a physical fire hose to reduce oxidative stress. That's what's going on with people with myocarditis right now. The sudden heart attack situation is actually being caused by fundamentally plasmalogen depletion of the heart from COVID. COVID specifically depletes your plasmalogens. It's a big deal. That's why we're having all these myocarditis situations.
What happens when your body's inflamed, that special bond plasmalogens that it mentions, a little bond called vinyl ether bond. It's basically like a fuse. It’s really like a fuse. It's designed to break first before something else goes wrong. Your body makes these plasmalogens and stores them in your membranes. Okay, so all these cell walls, okay, they're not just there to make you look pretty. They're actually physically got stuff in them. When you have an inflamed event, it releases these plasmalogens from the membrane and it just douses the fire. It's like throwing water on a fire.
Then once the fire is out, your body has to rebuild the reservoir. It's like having a lake next to your town. Fire happens, fire trucks come in, pump a hose into the lake and start pouring water on the fire. That's okay if you only use up half your lake and the fire is out and say, “Okay. Well, takes me two years to rebuild the lake, but it's going to gradually fill up again.” If you run out of water before the fire is out, now you're stuck with just a small trickle of water that's not enough to work. That's what's happening in some of these long COVID situations and other things.
It's a really powerful fire hose. This is what happens when you start getting – when these things decrease with age, they peak around our 40s and 50s. Then for numerous reasons, we start making less and less of them. Then as we make less and less of them, the body gradually adapts and tries to adjust to the different environment. Eventually, it can't adjust anymore and we have disease.
[0:34:59] SCOTT: In the book, you talk about the role of plasmalogens the cell membranes, in the nerve function arena. You also note that besides the brain, they're high in the heart, the kidneys, the lungs, the eyes, and that while they're mostly made in the liver, every cell in the body can make them and does contain them. Does increasing plasmalogen levels improve the health of the heart, the kidneys, the lung, the eyes and other parts of the body, in addition to what we see with cognitive function with the brain? Or is there a primary role in our health, more synapse neuron brain function? How broadly do plasmalogens support systemic health?
[0:35:38] DR. GOODENOWE: It's been so surprising. Since we're now in the world, right, and we have thousands and thousands of people taking plasmalogen precursors and the responses that we get back are far, far more diverse than originally anticipated, okay. First and foremost was then cognitive improvement. We published. We did a clinical trial. Got dramatic cognitive improvement in a relatively short period of time. Okay, that's how published in frontiers of medicine.
Clearly, brain fog, cognitive improvement, almost invariably improves. I really can't think of examples where people don't come back to us and say, “My brain awareness have improved.” And their family members. It's a very, very high percentage. That happens. Now when it comes to autism and the neural inflammation of the brain inflammation and the disruption of myelination that occurs with brain inflammation, that has been just really dramatic improvements in individuals.
This concept of inflammation of the brain and the ability to resolve it. It happens faster than we would have ever anticipated. That's not this really long months after months after months. People start seeing differences in weeks, in days even. It's really quite remarkable and unpredictable. If you hit the right button, you see dramatic improvements in individuals.
Then in terms of really acute care emergency room situations, where people are on a ventilator and they've lost oxygenation of the lungs, they start taking the proton glia, they make a nine. literally they leave the hospital in two days. It's hard to even get your head wrapped around. People will explain it with myocarditis long-term, they say, “I can actually feel it in my heart,” when they start taking. It's because we're not just poking. We're not tweaking something. It's actually a physical building block. It's physically sucked into your cells.
Yeah, so these things, so clearly as a general rule, the Omega-9 plasmalogen precursor, sleep, neurological calming, autism, MS, those type of situations, high percentage of people get significant benefit from it. Then the neuro is more of that activating the Omega-3. Improving neuromuscular function. Improving cognitive function. Improving mobility and energy and just awareness. That is the biggest thing people see. Yeah, it's a big deal. C-reactive proteins. As soon as you start taking the Omega-3 plasmalogens, if you have high CRP, it brings it down. Malondialdehyde levels, if your oxidative stress markers come down, your catalyzed levels come back up. It's pretty remarkable stuff.
[0:38:33] SCOTT: I was going to ask this question later and maybe not go too deeply into it. One of the researchers that I have talked to about plasmalogens has suggested that in autism and ALS, that plasmalogen levels are often already elevated. I'm wondering if that's something that you see as well. Are there certain conditions where plasmalogen precursor supplementation may not be advantageous, because maybe there are already elevations of plasmalogens?
[0:39:02] DR. GOODENOWE: Oh, that's a good question. It's important to remember that plasmalogens in your blood don't cross the blood brain barrier, okay. You can have high levels in your blood and that has no impact on the human brain for the most part, okay. When we're measuring blood levels of plasmalogens, we're measuring the excess output of yourselves. Some of the plasmalogens from your blood supply will go into your cells. Fundamentally, it's the other way around. The plasmalogens that are in your blood, they're coming out of your cells.
They're like the HDL system. When you have high levels of HDL cholesterol, it means your cells are really healthy, because they're making their cholesterol and they're exporting it and they're sharing it. They're putting energy back in the grid, so to speak. That's where that comes in. In terms of ALS, autism, so those are actually really, really different. I think you may even have multiple sclerosis. Diseases of mitochondrial failure, like MS and autism, what happens in those situations, is you have the mitochondrial function gets impaired and the mitochondria stop doing its job, or is unable to do its full job in the cell.
Parts of the other cells start taking over, or trying to help. That's when the peroxisome starts helping out the mitochondria. A whole bunch of palmitic acid and things that are supposed to go into your mitochondria, now go into your peroxisomes, and that turns on that peroxisomal function. Overactive peroxisome function in autism and MS is actually an indicator that the mitochondria are stressed. That will cause plasmalogen levels to go up in the blood, but that's not necessarily good.
It's a double-edged sword. It's good in certain aspects, but it's not helpful for the brain. In those diseases, autism and multiple sclerosis, those are white matter diseases. Those are diseases of myelin breakdown. The question is, how and why does the myelin get disrupted? The disruption of the myelination is caused by inflammation. It's caused by the microglia in the brain. This Microglial inflammation actually blocks, or stresses the oligodendrocytes in the myelination and it disrupts that myelination. Autism is a disease of impaired connectivity. It's a disrupted myelination process.
It's more of a global situation, where MS is a focal lesion-type process. It's the same biochemical concept. The omega-9 plasmalogens are very powerful in those diseases, because it’s like, this whole water and fire story I was telling you about. It's like, bringing in plain loads of water from the neighboring lake to help out. When you're taking plasmalogen precursors, you're actually saying, “Hey, here's some more. We'll supplement what your oligodendrocytes are trying to make. If we help, you can now catch up.” All of a sudden, this myelination gets back on track. This is what happens with the children while they start getting better, very dramatically with that. In MS, you can stop the demyelination phase.
ALS is very different. ALS has low plasmalogens. ALS has, it's actually, there's some mitochondrial component of it, but I have a number of patients with MS that we deal with, but their plasmalogen levels are really low. There's a peroxisomal failure. There's a whole bunch of other things to talk about for ALS, and copper transport and stuff like that.
[0:42:40] SCOTT: I know there is a difference between the omega-3 plasmalogen precursors and the omega-9 plasmalogen precursors. But just at a high level, what are some of the conditions where increasing plasmalogen levels may be a worthwhile exploration to improve health outcomes?
[0:42:56] DR. GOODENOWE: Well, cognitive impairment. Number one, brain fog, dementia, absolute Parkinson's, omega-3 plasmalogens are just hands down the first go-to in those type of situations. Cardiovascular disease, omega-3 plasmalogens, okay? If you've got oxidative stress, high levels of oxidative stress like Malondialdehyde elevation, or C-rector protein elevation, or you have low HDL levels, omega-3 plasmalogens, okay? Those will help improve your cholesterol transport, reduce your oxidative stress levels, improve your vascular function. Hands down, omega-3 for all.
All those, where you need to enhance function, okay? You need to turn the volume up of the system, the omega-3 plasmalogen, the DHA plasmalogen does that. For all your protective mechanisms, when the body is inflamed and you're saying, “Hey, I don't want to turn the volume up. I want to turn the volume down. I need to calm the system down. I need to calm the neural inflammation down. I need to calm down the optic neuritis, or a peripheral nerve issues.” Omega-9 plasmalogens, okay? Because those deal with –
The omega-9 plasmalogens, they restore the coating on the wire in your walls, okay? If you have a big inflammation going on and you're wiring in your walls is leaky and the signal's not getting all the way there and it's a bunch of noise, and that's what's causing the inflammation in your head is just – and you can't sleep. At least kids with PANDAS, or autism, inflammation is driving them crazy, right? You've talked about even bipolar and autoimmune related disease issues when you have autoimmune that is primarily a mitochondrial overload situation. Omega-9 plasmalogens dramatically improve that.
Core heart function, core lung function, when you're in that acute disease state, the omega-9 plasmalogen is really quite powerful in that core structural rebuilding process. They have a yin and yang approach to it. Normally, I recommend people take the omega-9 at night for the most time. It helps build overnight time. You sleep better. Then omega-3, during the morning. That helps activate you. Then you have this yin and yang. The human body has to have a controlled stress response for everything we do. It's a perpetual motion machine. Your body never stops. Your heart never stops. Your body never stops. All you can do is make sure that you are creating an environment that it's constantly adapting to a healthy situation.
[0:45:35] SCOTT: For listeners, we'll talk more about this later. The omega-3 plasmalogen precursor, that's the ProdromeNeuro product and the omega-9 plasmalogen precursor is the ProdromeGlia product. We'll talk more about that in a little bit. I wanted to just get an understanding around plasmalogens at different stages of life. From reading the book, my understanding was that in that 40, 50, 60 range is when plasmalogens are the highest. When we're younger, they're lower. When we get older, they start to decline. What is it that causes them to increase in that 40 to 60 age group? Then what is it that causes them to decline as we get older?
[0:46:14] DR. GOODENOWE: That's a really good point. Because when you're measuring things – this is the other part when we're talking about advanced interpretation of laboratory results, okay. Sometimes lab results are biomarkers. They're metrics for us to look behind the curtain. We need to infer from those results, like measuring. We’re measuring a blood sample, right? We're not measuring a piece of your brain, or a piece of your muscle. We have to infer as to how the body is resulting in these blood marker levels that we see.
There's an interpretation and understanding that comes in. It's a language. It's a very powerful language to learn. Plasmalogens levels go up for a different reason than people think. First of all, they're low when we're young. When we're born, we're actually born plasmalogens deficient. Okay, our bodies for the first six months, that's why breastfeeding is so important. The human body doesn't actually build up its own internal plasmalogen manufacturing capacity for the first six months or so. Of course, every child's going to be a little bit different, right? Some will be younger, some will be older. This is the way life is.
That's important, because that myelination in the brain is so critical. After about the first year, it catches up. Then we have the slow elevation in the blood going up. It's not because we're making more plasmalogens. It's because the lake, the reservoir gets full, okay. What you're measuring in the blood is the overflow from the lake. If the lake is full, and we continue to myelinate it, this whole reservoir, which is all the white matter of your brain, all the white matter of your tissues, your body's been making plasmalogens ever since birth. It's been filling it in the membranes, plugging it in here, plugging it in there, and it's building up over time.
Then at some point, you get more and more full, right? If you're still making plasmalogens, if you're making plasmalogens and the reservoir is full, then you're going to see a larger spillover into the circulation saying, “Hey, excellent. Okay. You're making more than the lake needs, the reservoir needs.” Then eventually, what happens is you stop making enough. When your plasmalogens and the blood go down, that tells you that, “Hey, okay, the lake's being drained.” Now, the water going into the lake, a lot of that's being used up. The lower the plasmalogens start trickling down in your blood, that tells you that the bigger drain that's occurring on that system. That system's getting drained more and more and more.
The delta, so what happens is the lower your plasmalogens are in your blood, that tells you how quickly the lake is running dry. That's why it predicts the rate of cognitive decline. Low plasmalogens don't just predict dementia in the elderly population. It predicts the rate of decline of that dementia. It predicts the rate of death. The time to death is predicted based upon level. It's a quantitative prediction model. It's because when it's too – the lower it is, it just tells you how quickly you are declining.
That's where the blood levels are. That's why it peaks. The reason why it peaks in our 40s and 50s is because we've been myelinating. If you've maintained your health up to that level, okay, you're good, your muscles, your heart, they're basically full of plasmalogens. Our brain is still myelinating. The white matter of our brain is still increasing in our 40s and 50s. That means you're full. Then at some point in time, reduced mobility. We don't move as much later on in life. A bunch of other things that contribute to that normally stimulate plasmalogen manufacturing decrease. With time, you have the increased risk of adverse reactions from drugs. You're taking this and that and the other thing, and they all have little death by a 1,000 cut type effects on your system.
[0:50:25] SCOTT: What are some of the factors then that might lead to lower than optimal plasmalogen levels over time? Is it aging? Is it environmental toxicants, other cellular stressors? Are there ways to optimize maybe our peroxisomal function and plasmalogen production endogenously, without relying solely on the use of exogenous plasmalogen precursors?
[0:50:50] DR. GOODENOWE: Yeah. The biggest drivers of plasmalogen manufacturing and the biggest reasons why they decrease with age, or in other circumstances is two things. One, the failure to maintain a fasting state of the human body. Okay, so plasmalogens are made in peroxisomes. The human body is designed to run a fasting state. We eat a meal simply to refill our fat cells, and then we run off of our adipose tissue for the rest of the day. That's how the human body is supposed to operate. When you're in the fasting state, your body is running off of fatty acid energy from your fat cells. That's when the peroxisomes are in full form and they make plasmalogens during that period of time. You also make your cholesterol. You do regulate all your hormones. That all occurs when your body's in the fasting state.
When you're in the fed state, you're all running on glucose, pure mitochondrial function. Number one, this late-night eating, eating all day long, high glycemic food type diets all reduce the number of hours per day that your body's in a fasting state. The second one is muscle atrophy. Okay. The skeletal muscle system, your body is designed to have a certain amount of skeletal muscle, certain amount of non-skeletal cellular systems. Your skeletal muscle runs on fat, okay. Your heart, your skeletal muscles, they're primarily, they run on fatty acid energy, not glucose energy. They are big contributors to plasmalogen manufacturing.
That's why resistance training has such a powerful effect in dementia, for example. Fasting and resistance training, two of the most powerful things that you can do physiologically to improve cognition and reduce dementia rates, are the two most pro plasmalogen producing behaviors that you can do.
[0:52:49] SCOTT: That's awesome. Love that.
[0:52:51] DR. GOODENOWE: Those are the two main factors.
[0:52:55] SCOTT: When we think about Alzheimer's, we look at the Bredesen recode framework. There's multiple subtypes, including the inflammatory, atrophic, glycotoxic, toxic, vascular, and traumatic subtypes. There are many holes in the roof that contribute to cognitive decline, as Dr. Bredesen teaches. Many of these are what we would think of as more root causes. In your book, you suggest that plasmalogens may be a cure for Alzheimer's. Does this mean that the plasmalogens are addressing the root causes, or holes in the roof? Or are they instead not allowing these insults to damage the structures in the brain that are involved in cognition?
I know in the book, you say health is not the absence of disease, but the maintenance of functional reserves. In other words, not waiting for the gas in your car to run out and the engine stopping before you refill the tank. Our plasmalogens essentially bypasses, such that even if someone has infections, maybe viruses, or other toxicants, such as mold, or mycotoxins that could lead to Alzheimer's, that they're essentially shielded from the damaging effects from the plasmalogens.
[0:54:03] DR. GOODENOWE: Well, the simple answer is yes, for that. It's all diseases are a combination of two components. One is the susceptibility that the person has for the disease. The other one is the strength of the stressor that's being put on the human body, okay? It's like a bald tire versus a brand-new tire. You can have a brand-new tire, but you can still get a flat. If you hit a big enough nail, the best tire in the world is going to go flat, okay? Probabilistically speaking, it's going to be less likely than a bald tire.
With a bald tire, just a little rock can make you flat tire. The outcome is a flat tire. In order to get a flat tire, two things have to be combined. One, the stressor has to be greater than the resilience of the system. I can now say, “Oh, hey, I got a bald tire. I'm going to go make sure I go around. I'm going to sweep all the roads in my city so that I make sure I never drive over a nail.” That's the remove all possible negative situations. I want to make it so that it's safe for me to drive on bald tires. That's the remove all disease-causing mechanisms approach.
That is fundamentally good, right? You've reduced that negative stressor on the system. The other side of it is that people forget, even with cancers, or anything, those type of cells, the number of cells that are actually unhealthy are a very, very small fraction, versus all the cells that remain in their health. By increasing the strength and resilience of the surrounding cells, you can shrink cancers. It's a matter of commandeering the rest of the body to make it inhospitable for these negative influences to occur.
Doesn't mean these negative influences aren't real, because we can do the science and we say, “Hey, it's there. If you have this infection, you're going to have this outcome.” That's all true. The question now though is that once you remove those negatives, it's dependent upon the human body's underlying resilience that determines how well you recover from it, okay? Because you're removing a negative and the underlying system has to bounce back. A lot of times, you can actually fix the underlying system and these other problems just disappear. Vascular flow rates to the brain, for example, if you want to look at neurovascular coupling, you can do all this by MRI and so on, so forth.
Anyways, the answer to that question is, yes, my fundamental belief is that for all of these stressors of the human body, the first good example is take COVID, or take something. Not everyone with COVID dies. The fact that certain humans can be exposed to a stressor and still thrive under that exposure level tells us that increased resilience is always a stronger clinical program than removing toxins.
Animal models for demyelination, cuprizone, for example. Highly toxic, highly reproducible demyelinating stressor. If you give animal plasmalogens and then you give them cuprizone, they don't demyelinate. In the presence of a completely well-documented, absolutely nasty, nasty demyelinating stress, if these animals have the plasmalogens, it's like, they don't even have cuprizone. It turns it into candy. Or MPTP, which we use for killing dopaminergic neurons in Parkinson's disease. If the animals have the plasmalogens before the MPTP, okay, it doesn't kill any dopaminergic neurons. Those things tell us that underlying resilience, okay, pound for pound has a much stronger window of utility than chasing after every single possible bad thing that could be affecting my life.
[0:58:16] SCOTT: My takeaway from that was that plasmalogens are essentially, a way to increase our vitality, or to raise our vibration.
[0:58:27] DR. GOODENOWE: Yeah, exactly.
[0:58:29] SCOTT: Dr. Bredesen's talked about APP, or amyloid precursor protein as being key in the development of Alzheimer's, that we can either be in this building, or a blastic state, or breaking down, or a plastic state. Are plasmalogens then impacting the expression of APP and influencing whether we move in a building, or breaking down direction?
[0:58:51] DR. GOODENOWE: Yeah, so APP, amyloid precursor protein is a critically important protein for human life, okay. For an example, it is not possible to develop APP negative animal models, okay. Life cannot occur without APP being present. It's an absolute requirement. Amyloid precursor protein, APP, gets processed by two different mechanisms. One creates what's called secreted APP alpha, sAPP alpha. That is one of the most powerful neurogenic stimulators in the brain. It's a drug. It's an amazing molecule itself. It comes directly from APP. When APP gets metabolized by an enzyme called alpha secretase, it creates this sAPP alpha, which is one of the most powerful neurogenic for neurogenesis. The human brain needs that to grow and develop 100%.
That's what 90% or more of APP is used for. Maybe 95% or more of APP gets converted to soluble APP alpha. The toxic part, or the negative part is the beta amyloid. That's when APP gets processed by beta secretase. That is a small component of the APP cascade. These two enzymes exist in two different parts of your membrane. The alpha secretase is in the fossil lipid-rich region, which contains the plasmalogens. The beta secretase is in the, what's called a lipid raft region, high cholesterol, sphingomyelin zone, okay, the dense part.
When we age, what happens is we lose plasmalogens. The amount of our membrane that becomes high cholesterol with rafts increases, and the amount of our membrane that becomes this fossil lipid-rich region decreases. What happens is the amount of soluble APP alpha decreases. The amount of beta amyloid increases. Plasmalogens, so people with high DHA plasmalogens, they have low amyloid and they have high alpha secretase activity, which gives them high neurogenesis capacity. That's where the body wants to stay healthy.
Then people with low plasma allergens have high beta secretase. The other flip side of the coin, the other reason why we know so much about this is because of the genetic predispositions, say the APOE4 alleles. You have the E2 carriers, E3 carriers, E4 carriers. These three types of alleles affect this cholesterol efflux rate of neurons. That affects that lipid raft composition and directly affects the alpha secretase to beta secretase activity. Neither one of them have anything to do with Alzheimer's, fundamentally. Amyloid has absolutely nothing to do with Alzheimer's, or dementia. It's just a bystander on the road watching an accident happen.
[1:01:56] SCOTT: Let's talk a little bit about the APOE4. Often, this APOE4 predisposition is almost itself perceived as a death sentence for people mentally, and then possibly even epigenetically influencing gene expression. They can often feel very hopeless when they find out that they have this predisposition. Talk to us about how higher levels of plasmalogens might mitigate APOE4 status. Can we neutralize that genetic risk factor? Are the plasmalogen levels potentially even more deterministic of cognitive outcome than the APOE4 itself?
[1:02:32] DR. GOODENOWE: Yeah, absolutely. First of all, APOE4 itself is actually not a risk factor for Alzheimer's disease. I repeat that. APOE4, statistically, is not associated with Alzheimer's disease if you measure its downstream effect, okay, which is the amyloid formation. This is just straight up, hardcore science fact. If you take the brain, the post-mortem brain analysis of individuals with different levels of cognitive impairment and you measure brain pathology with their genotype and their biochemistry, you will find that if you don't know anything about the brain of the human being, APOE4 is predictive of dementia. People with APOE4 genotype will have twice the rate of dementia than someone without. That's a fact.
Then if you take a look at the people, then if you say, “Okay. Why do I measure brain amyloid levels?” Because see, not everybody with an E4 genotype has high brain amyloid. Some do, some don't. What happens is that people with an E4 genotype are more likely to have brain amyloid than someone without an E4 genotype. Then if you say, if I look at brain amyloid levels, and I also ask the question, okay, what's more important? Brain amyloid, or your E4 genotype? Then you find out that the E4 genotype has no relationship at all to dementia, or cognitive impairment if you know the amyloid levels. Because all that's important is APOE4 has some sort of prediction as to your amyloid levels. Once you measure your amyloid levels, I don't need to know your E4 status.
Okay, then, so now we have amyloid levels. Okay, we say, okay, well, amyloid levels, if I don't know anything else about the human brain, amyloid levels are associated with reduced cognition. What happens if I know other things about the cellular health of the brain? If I know the neurofibrillary tangle levels, or I know the phospholipid levels, okay, or lipid raft levels, then you find out that if you know that part of the brain, amyloid has that zero association with cognition.
Okay, people have high levels of amyloid. If they have healthy levels of plasmalogens, though amyloid has zero association with cognitive impairment. This is straight up fact. The point of the story of this is that the APOE4 genotype has certain biochemical risk factor associated with it, okay? That is silent until that risk factor occurs, which is the amyloid. The reason why APOE4 shows up as a risk factor, you're not getting Alzheimer's in your 20s with an E4, right? You're not getting it in your 30s. Okay, what APOE4 does is it moves the aging curve back, okay. That's all it's basically saying from a – and the aging curve is being driven by this plasmalogen depletion.
As your plasmalogens decrease, E4 becomes a bigger risk factor, because you can't – it's more dependent upon the plasmalogen levels than an E3 carrier, or an E2 carrier. If you restore the plasmalogen levels in the brain, E4 has no risk association with dementia anymore. This is where biochemistry comes in. Things have a reason behind them, okay? It's a causation. I tell, I know on a tangent to some people, that's how these statistics work out, it's like saying, okay, I use this analogy in the book. Statistically. I say, you know what? 50% women get twice as many scalp rashes than men. Say, that's a fact. We don't know why. Well, why? Why is it that women getting these scalp rashes? Why are they getting versus men? Is it because they're double X chromosome? Is it because they got estrogen? What is it about being a woman that's giving these women head rashes that men don't have? What is it about being a female?
Then someone says, “Hmm. You know what? I found out that women use hairspray twice as much as men do.” But not all women use hairspray and some men use hairspray. Then I say, “You know what? Let me just look the question of the rate of scalp rashes in hairspray usage.” They say, “Wow. Once I do that, it makes no difference whether you're a man, or a female. It determines whether or not you're using hairspray or not.” It's a hairspray that's actually causing the head rash, not the fact that you're a girl, okay. Just the fact is that twice as many girls use hairspray, so twice as many girls get the head rashes. It has nothing to do with you being a male or female. It has to do with your hairspray usage.
Then you can go further down and say, well, is it all hairsprays? Or is it just some hairsprays that are causing the head rashes? Then you can find out, well, you know what? Here is the one toxic molecule that's causing the head rashes. It has nothing to do with your gender. It has nothing to do with the hairspray. What's going on is this element in this. APOE4 is like that, okay? It's saying, okay, clearly twice as many people before get Alzheimer's versus E3s. That's a fact. The question is, why? Okay. What is it? What is the reason behind that? If you know the reason behind it, then you can counteract it.
The reason behind it is that E4 has a cholesterol clearance rate difference, okay? They're cholesterol savers. They are more dependent upon the other compensatory mechanisms that most young people all have. That's what understanding these genetic risk factors are. Same thing with a bracket genotype for breast cancer and ovarian cancer. Its question is, why? What is the biochemical mechanism of that reality? That's where biochemistry comes in as giving us actual real solutions to solving these problems.
[1:08:48] SCOTT: There are those people that think that amyloid is a cause of Alzheimer's. I think more and more people are understanding that that may actually be the body's response to another insult and infection that amyloid may actually have beneficial properties. Anti-microbial properties, for example. I'm wondering, will increasing plasmalogen levels prevent an unnecessary high level of amyloid accumulation? Or will it also reverse that, or lower it once present? Could it potentially reduce the amyloid such that we're removing some of that protective mechanism of the amyloid when we still have a fire that's actually in play?
[1:09:30] DR. GOODENOWE: I really don't have a sensitive way of saying this, but that's just adolescent fantasy. I'm sorry. Look, amyloid is a good biomarker of the brain. You shouldn't have it in the brain. No one's going to say, “Oh, amyloid's good for you.” No, it's not. It shouldn't be there. The reason it's there is strictly because of cholesterol regulation of the membranes, period. It has this idea of trying to find some positive nature that there's some stimulatory sponge activity. That is just pure scientific fantasy. I'm sorry, there's no polite way of saying that.
[1:10:11] SCOTT: No, I love it. Don't be sorry.
[1:10:13] DR. GOODENOWE: Because it's not true. People have to realize that nature abhors a vacuum. You can't have a hole in your head. If you have a hole in your head, it's going to get filled with something. When you get brain atrophy, when you have – amyloid will fill in those cracks, or other things. This is where you get this opportunistic infections of the brain. If you have a void, something's going to fill it. These type of situations are, first of all, amyloid is a great biomarker of the brain. Don't get me wrong, I think it's a wonderful thing to look at, because it's a good measure of membrane structure and function. It's a great biomarker of that.
Having low brain amyloid is a good indicator of good brain health. Absolutely. Same thing with neurofibrillary tangles, it has a different mechanism. Yeah, but in terms of its causation pathway, amyloid is not toxic. We've known this since the 90s. Big studies by Brack and Brack, this is not up for question. The only time it happens, if you pump someone with massive levels of amyloid, okay, yeah, you're going to have an adverse event. In the average aging population, it is not causative of Alzheimer's. Of dementia, dementia. It's obviously Alzheimer's. That's the definition of Alzheimer's is tangles and plaques. That's what Alois Alzheimer discovered in 1906, or whatever it was. That's clearly Alzheimer's, but the cognitive impairment part is not related to amyloid.
[1:11:44] SCOTT: Do plasmalogens have an equally beneficial effect in Alzheimer's, vascular dementia, Lewy body, frontotemporal dementia, and does increasing plasmalogen levels have a similar effect in terms of symptom improvement in subjective cognitive impairment, mild cognitive impairment, dementia, and Alzheimer's? Or do we need to intervene early in the process to get more obvious benefits?
[1:12:08] DR. GOODENOWE: Well, we find short-term benefits more in the heavily demented people, quite frankly. It's the opposite. We actually see positive effects faster to a greater degree, the more demented the person is. Because there's more of a window of improvement.
[1:12:26] SCOTT: Okay.
[1:12:28] DR. GOODENOWE: MCI’s a little more difficult to deal with. MCI’s unknown cognitive impairment. Maybe it is. Maybe it isn't. People toggle back in and out of it, type of thing. When people start getting to a mild to moderate dementia, they don't revert. They don't just normally just get better randomly, okay? A certain percent will, because it'll be some biological underlying cause with it. Fundamentally, that means they're on a fairly well-defined timeline at that point in time.
Age-related cognitive decline is clearly where the plasmalogens have the greatest impact. You're always going to have mixed pathologies in the brain, okay? This idea that you have, Alzheimer's dementia, and you have Lewy body dementia, and you have vascular dementia, and you have one versus the other, that again, okay, is academic fantasy. It just doesn't actually happen that way. You have mixed pathologies, okay? It's extremely rare. You have very small percentage of people that will have just amyloid pathology in the brain, okay, for example, or just Lewy body. One will be a greater contributor versus another, but it doesn't occur that way. The brain health decreases, and you get multiple pathologies in the brain, okay? Not just one.
In terms of the cognition process, once you understand the cognitive process, it actually is related to the cholinergic system, okay? Then it's really irrelevant from a symptomatic perspective what the underlying causation was, okay? The answer is it works equally in all factors.
[1:14:11] SCOTT: You mentioned the vholinergic neuron system. It's responsible for cognition. The release of acetylcholine involved in creating and retrieving memory, reduced mental function can be caused by a reduction in acetylcholine neuron transmission, reduced muscle function, sarcopenia can also be related to acetylcholine neuron function. How do DHA plasmalogens impact the cholinergic neuron function?
[1:14:36] DR. GOODENOWE: Yeah, so the cholinergic neurons are really the canary in the coal mine of neurological decline associated with plasmalogen deficiencies, okay? When you have a plasmalogen deficiency, it's clearly affecting all parts of the brain. It's affecting the GABAergic system. It's affecting the glutamatergic system. It's affecting all systems, because that synaptic function that I was telling you about, that's every single neuron in the brain functions that way.
The question is why does there appear to be a selective, or accelerated decline of the cholinergic system? What makes the cholinergic system somewhat different and more sensitive to a plasmalogen deficiency than other neuron systems? That falls into how the cholinergic neuron regenerates its pulsing activity. That's how choline gets taken back up into the neuron, repackages acetylcholine. That is unique, there's a unique mechanism in cholinergic neurons that is highly dependent upon membrane structure. This is that reuptake of the choline.
The reuptake of the choline occurs through this choline high-affinity transporter. That transporter only gets expressed during vesicular fusion. Whereas, the serotonergic neuron, or dopaminergic neuron, the proteins that suck the dopamine back up after a nerve impulse, they're always sitting there, okay? They're just sitting there waiting for a dopamine molecule to suck it back up.
Cholinergic system doesn't do that, because choline is a nutrient. Choline, all your cells require choline. Not all your cells get dopamine. Just dopamine neurons get dopamine, right? The cholinergic cells have developed a system that says, “You know what? I can't suck choline up from all over the place simultaneously. I need to have an activity dependent uptake system.” The cholinergic neuron is when the neurotransmitters get released, that's when the uptake protein gets expressed.
What happens in plasmalogen deficiencies is that this synaptic neurotransmitter release is impaired. That doesn't just affect the release of acetylcholine into the synapse. It affects the uptake of choline back into the neuron. Plasmalogen deficiencies have a double whammy on the cholinergic neuron that doesn't affect the other neurons as much. That's why we see this – the first, the canary in the coal mine, is this reduced cognitive functioning with plasmalogen deficiencies. That's why there's such a strong correlation.
[1:17:14] SCOTT: I want to talk a little bit about the cholesterol connection to plasmalogens. In the book, you say that cholesterol and phosphatidylcholine are the yin to polyunsaturated fatty acids containing ethanolamine plasmalogens, which are the yang. Higher cholesterol and PC result in stiffer, more rigid membranes, higher PUFAs result in more fluid membranes. It sounds like, we need both the cholesterol and PC, as well as the plasmalogens, but also, sounds like, maybe beyond being yin and yang, that maybe there's also some counter influence there in terms of membrane fluidity. What is the ideal cell membrane state?
[1:17:54] DR. GOODENOWE: Yeah, that's a really good point. Remember, phosphatidylcholine is another thing that I'm a big – That's another big deficiency as we get older that really affects our health. Because it drives a reverse cholesterol transport system dramatically, so you choline levels and low choline, high – Virtually anyone that gets pancreatic cancer has a choline deficiency. Lots of cancers associated with this thing. Choline deficiencies are a big deal. One of the biggest deals about them is their effect on the cholesterol system.
This is again when it comes down to interpreting blood results appropriately. Because when we talk about the membranes, it's the membrane – We're not measuring membranes in a blood test. We're measuring the general equilibrium out there. That's why high HDL, moderately good cholesterol in their low 200s is an indicator that your cellular regulation is in proper condition, which means your cells are making cholesterol and they're exporting cholesterol. That means, and if your cells are exporting cholesterol efficiently, that means that the cholesterol in your membranes are not being built up, okay? That's why low cholesterol is actually a bad thing, because it's telling you that your cells are not releasing it.
That's why specifically, low HDL is a very, very bad risk factor for so many different things. Because if you have low HDL levels, that means your cells are trapping cholesterol. When the cholesterol builds up in the membrane, the membrane gets stiffer, and proteins don't work properly, and that's where it goes in. That's where the cholesterol phosphatidylcholine in membrane process that creates a stiffer membrane. It's driven fundamentally from impaired cholesterol regulation, right?
Your membranes of your cell are like the thermostat on your wall. Your body regulates how much is in there. When there's too much, it turns on the air conditioning. It says, “Okay, let's get rid of some of this stuff.” It's too little, it turns on the other – Your body has to continually adjust that. It's when that thermostat stops breaking down, when the body can't adjust, that we have problems. That's where the cholesterol –
The polyunsaturated ones, they deal with this other cholesterol efflux. The cholesterol acyltransferase system. That's why the polyunsaturates improve membrane fluidity and help compensate. They work together. Because everything in your body, your body has a backup plan and a backup plan of the backup plan for a lot of things, right? There's redundancy built into the system. That redundancy is not absolute. Not everything has a complete compensation mechanism.
[1:20:39] SCOTT: I think we know the answer to this next question, but I just want to ask it anyway to tie these concepts together. Dr. Patricia Kane has been a mentor of mine over the years. She teaches about lipids and cell membranes, and promotes the use of phospholipid replacement, as well as other fats to balance the health-supporting lipids in the body. Is there an overlap between her approach, which is the PK Protocol and the plasmalogens are phospholipids, such as phosphatidylcholine, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl anositol? Are those synergistic with plasmalogens? Do plasmalogens have any properties, like some of the other lipids that maybe they're helping to support the body in terms of detoxification, for example? What is that overlap between these two lipid optimization approaches?
[1:21:29] DR. GOODENOWE: Yeah, they're very complementary, because they're both part of the membrane structure. The phosphatidylcholine system really is a big deal. It should not be underestimated. We have serious choline deficiency issues in the general population that should – that have negative consequences. The reason for that is choline is energetically demanding to make through the methyltransferase system. Low choline levels are associated with high homocysteine, and other things.
The choline supplementation strategy, absolutely 100%. As a phosphatidylcholine choline mechanism. The IV- phosphatidylcholine, the brand name of one of these things is they call Plaquex, or whatever it's called. It clearly improves reverse cholesterol transport, because that reverse cholesterol transport, the HDL system requires phosphatidylcholine, an enzyme called LCAT, lecithin cholesterol acyl transferase. When cholesterol leaves a membrane, it comes out cholesterol in the free form. It's phosphatidylcholine that donates the fatty acid to it that goes under the HDL particle. When you're phosphatidylcholine deficient, when you have people with phosphatidylcholine deficiencies, they'll often have low HDL levels. Because the body, because the low phosphatidylcholine is not allowing the system to work normally. The phosphatidylcholine system is important.
The other thing about phosphatidylcholine that’s important, it's one of the few phospholipids, like as a lysophospholipid, that'll actually cross the blood-brain barrier. Most lipids in the body will not cross the blood-brain barrier. Ethanolamines, serines, these things don't go across the brain. The brain, makes them themselves. Lysophosphocholine will get through the blood-brain barrier on the CSF side. The other one is the plasmalogen precursors, so triglycerols. Alkylglycerols and triglycerols, they will pass through not as a diacylglycerol, or any alkylglycerol. Those are one of the two main mechanisms for us to get fat back in the brain. That's why the phosphatidylcholine system is good.
The detox, or the inflammatory component, the HDL, the phosphatidylcholine system contributes to that, but the real hammer is the plasmalogen reducing the membrane peroxidation. Because the phosphatidylcholines and those things, they don't change. They're not direct detox in terms of peroxidation of membranes, which are immunogenic. They're detox in the sense that they help increase HDL, help clearance, help that process. That's the main issue. Then restoring the balance of the pro-inflammatory and anti-inflammatory polyunsaturates, when you have inflammation of your body, enzymes called phospholipase A2s, they break down membrane phospholipids and they release the fatty acid, the sn2 position. They have different cascades. That's why highly reproducible data, the DHA, the arachidonic acid ratios have an important impact on outcomes of inflammation.
[1:24:27] SCOTT: So many dots that you're connecting. This is really amazing. Just to make sure that I'm clear, so it sounds like plasmalogens do have a role in supporting detoxification in our systems.
[1:24:37] DR. GOODENOWE: Mostly because of the reducing the immunologic signal of – When you have a toxic situation, cells become peroxidated. It's the peroxidation of the membrane oxidize – it’s oxidized lipids that really drive the inflammation and the immunogenic cascade, regardless of what the underlying cause. Whether it's COVID, whether it's a bacterial infection, whether it's – whatever it is. Ultimately, the peroxidation of the membrane is what signals the immune system, say, “Oh, something's wrong here.” Plasmalogens are direct neutralizers of those peroxidative membranes, because of the vinyl-ether bond. That's where they contribute to the main inflammation detoxification process.
[1:25:23] SCOTT: You suggest that a cholesterol in the 220 to 240 range with an HDL and the 60 to 90 range is healthiest. You note that those with higher HDL to LDL ratios have higher cognition, lower dementia. We know that high membrane DHA plasmalogen levels enhance cholesterol efflux, help to inhibit unhealthy APP processing can impact the lowering of amyloid. Higher plasmalogen levels lead to lower triglycerides, but higher cholesterol. I’m wondering if you can help us understand this improving cholesterol efflux and higher cholesterol levels with higher plasmalogens, and if someone with a cognitive issue already has high APOB, high small density LDL particles, an overall elevated lipid picture, could plasmalogen precursors potentially make things worse? Or will they in the long run, help to balance that lipid picture?
[1:26:20] DR. GOODENOWE: They help balance the picture. I take a fairly simplistic approach. It's easy to get really into the weeds on some of the stuff, because scientists love to do that. I've done it myself. Really, I just look at total cholesterol levels and HDL, to be honest with you. These ratios for statistical studies and papers will do them more fancy like that. For the average everyday person, you want to have healthy total cholesterol levels in the low 200s. As soon as it gets below 200 for total cholesterol, your all-cause mortality starts going up, period.
Your HDL level should be in that 60 to 90 range. When it gets down to 50, certainly when it gets down below 50 in the 40s, a whole bunch of risk factors come in. It just relates to two simple things. It's that the HDL tells you that your cells are making cholesterol and exporting them. That's what it's selling. It tells you that your reverse cholesterol transport is working. If it's low, you want to look for whether your phosphatidylcholine levels are low, or your plasmalogens are – that'll also contribute those two things. Or niacin is another big thing, your NAD level. Niacin is another big HDL contributor. That's the thing. The triglycerides indicate that you have good peroxisomal function, but you have good fatty acid metabolism. You want to keep it under 100.
When triglycerides get over a 100, it indicates that either your mitochondria, or your peroxisomes are not properly metabolizing fatty acids. Fundamentally, just that's all it means. The question is, is why? Is your mitochondria stressed, or are your peroxisomal function being impaired? Which is why resistance training, fasting, diet, all these things, you'll notice that they all have very similar general outcomes. Triglyceride lowering, HDL elevating. Over and over again, you'll see that pattern.
If you see anything out there that you see that does those two things from a nutritional perspective, or a behavioral perspective, that's good. That means that it's helping regulate the body's energy balance. Yes, that's where plasmalogens come in. They’re peroxisomal stimulating and cholesterol supporting molecules.
[1:28:30] SCOTT: You talked about the minimal impact of diet in terms of plasmalogens that we're not necessarily getting them from the diet. We're not really absorbing them from the diet. In terms of overall lipid picture, are there any dietary ideas, or strategies that you have, like olive oil, for example, you mentioned in the book. We talked a little bit about fish oil. What other lipid optimization should we be considering from a dietary perspective? Does that really have any role then in terms of our endogenous plasmalogen in production?
[1:29:04] DR. GOODENOWE: Yeah. The endogenous plasmalogen production is really driven from a dietary perspective in terms of your maintenance of your fasting state, and making sure that you have proper B vitamin nutrition and so on. Proper supplementation of those situations. The nutritional availability of plasmalogens is virtually non-existent. The reason for that is that when your body makes plasmalogens, the final step creates is vinyl-ether bond. It's designed specifically to neutralize peroxides. It is designed to be super, super sensitive to peroxides. It breaks, it neutralizes it. It gets blown apart. It gets broken down by acid.
When you eat a nice, juicy steak, or you eat an animal product that has plasmalogens in them, as soon as that hits the hydrochloric acid of your stomach, they're gone. They don't make it past the stomach, or the upper intestine. Because your stomach is concentrated hydrochloric acid. It's there to protect you from bacteria and other things. Yeah. Stomach acid is the first line of defense of human digestion. It destroys all these plasmalogens, full stop. That's why human breast milk doesn't have plasmalogens, it has plasmalogen precursors. Okay, it has these alkylglycerols. That's what's in human breast milk. They survive. They're untouched by the acid in the stomach. They go right into the blood supply and into your brain.
[1:30:27] SCOTT: Which is also true of the supplements that you have formulated.
[1:30:30] DR. GOODENOWE: That's exactly right. Dietary, I'm a big fan of a balanced diet. I don't really like a bunch of fats. I think the time restricted eating is important. I think you should have a high protein diet, good fat, like the egg oil type fatty meats with some, with some decent fiber, or vegetables. Basically, I'm a meat and low glycemic index vegetable guy. Then if you need to have a bit of a snack, if you're taking your supplements in the morning or at night, just make sure it's a nice high protein, high fat snack, basically.
Then you can live your life. You don't have to get super crazy. If you have other things that you're doing in your program. And have a variety of your diet. Because remember, nobody knows all the answers to this stuff. They had to remember, we're all guessing to a certain degree on some of this stuff. You have to fuzzy some stuff in there and realize, okay, there's a reason why good diverse diet happens, because you might be getting something from one nutrient versus another that you, and you just need – you might need it a little bit here and there. Keep your diet balanced, but within that range is my general rule of thumb. Then you can also enjoy your life, too.
[1:31:44] SCOTT: I was recently listening to a lecture from Dr. David Musnick, who is an expert on traumatic brain injuries. He commented in that talk that plasmalogens was an area that he was just starting to explore. Wondering, do plasmalogens play a role in those with traumatic brain injuries?
[1:32:01] DR. GOODENOWE: Absolutely. Especially in omega-9. It's pretty much a concussion prevention molecule. If you have a kid playing football or hockey, I would be recommending taking proton glia two hours before every game, because you want to have that present. Concussion is a brain inflammation event. Yeah, absolutely. The biggest things for concussions are make sure we get blood flow to the area of insult, because that's the other part of the brain. The brain's got to fix itself from the inside out. When you bruise your shoulder, you've got lots of circulatory system that can actually remove that stuff. Your brain does not have that level of circulatory system. Every study on earth that has increased blood flow to the concussed area improves TBI outcomes, period, full stop. If you can improve the circulatory system in the area of the concussion, you get better improvements. Absolutely.
Second part is from the inside of the brain. That inflammatory component is really a white matter issue. Most people with concussions don't recover from the concussion. They adapt to the concussion. The neural inflammatory component of the concussion lasts a very, very long time. It can last forever. What happens is when you get these athletes, we give them the return to play designations, the inflammatory component of their brain hasn't actually gone away. They have just mapped around it. They have adapted to it. That's why we have these longer term – that's why secondary concussions, or that's why we have these long-term effects. Especially if you get a big head injury in children, okay. You might not notice the difference for 10 years.
These other psychiatric diseases that are associated with early head injuries are quite a large number. Head injury is a very interesting thing. Yeah, plasmalogens are critical, because that's inflammation of the brain, making sure you can restore that membrane myelination process is core. Absolutely core to concussion research and prevention.
[1:33:59] SCOTT: Through your company, Prodrome Sciences, you offer the ProdromeScan. I'm wondering if you can talk to us about some of the key insights that one might gain from that. What does the test really measure? Why did you select some of those specific measurements as indicators of health?
[1:34:15] DR. GOODENOWE: Yeah, so the ProdromeScan test is like your Biochemistry 101. It's for doctors that have had all this diagnostic experience with the basic blood testing. It teaches them how to interpret human biochemistry in a more comprehensive, holistic way, and understand how the pieces fit together. It selectively deals with the real core issues. We talk about membrane structure and function. The membrane structure, the phospholidcy, ethanolamines, plasmalogens, cholines are laid out. We can see how that phospholipid metabolism of the human body is working.
Then it looks at the fatty acid distribution. Not total fatty acid, because when you're looking at total fatty acids in red cell membranes, and so on, so forth, you're dealing with – you're not dealing with the active fatty acids. Things are mixed in there. We actually measure fatty acid distributions actually on the phospholipid backbone. It's actually phosphatidylcholines, and we measure the individual fatty acids and look at the core ratios to make sure that that is – because that's what's actually happening when you get a phospholipase A2 event. That's actually what's being generated in the human body, and we can optimize that.
There are certain gut microbiome metabolites called GTAs that are very, very potent anti-inflammatory, very potent anti-cancer molecules. When they're low, they're highly predictive of future colon pancreatic cancer. We measure those simply. Anemia, especially in younger people, you want to keep an eye on that. Then methyltransferase function, we look with homocysteine. This is one of the really core systems of human physiology that is a weak link. That's why people are taking homocysteine lowering meds, or supplement, but it's really what methyltransferase system. It's making sure that you have, and then look at the sphingomyelin and the ceramide ratios. We get a better picture of the fact is, is your body got proper methyltransferase capacity.
Then mitochondria function, we look at mitochondria leakage, because if mitochondria aren't working, you see a quay leaks out and goes into fatty acid elongation, so we measure that. Peroxisomal function, looking at the plasmalogen ratios, and also the DHA, the EPA ratios, tells how peroxisomal beta oxidation is working, and then your simple fasting triglycerides. You get a sense of that in combination with the mitochondrial function, cholesterol transport, HDL, total cholesterol, that type of thing.
Then we look at oxidate, uric acid and creatinine. I use creatinine – the traditional use for it is for kidney clearance. I'm more concerned about sarcopenia and muscle wasting. Big issues. Creatine deficiencies are big issues. People get these low creatinine levels. I’m much more concerned about low creatinine than high. Obviously, if you have high, you have kidney issues that you deal with those situations. Those low creatinine is a big problem for people that try to stay young long, you need to be on your creatine. You need to make sure that you don't become creatinine deficient, which means you're basically muscle wasting. People don't even know it. They think they're doing all the right things and they're wasting away.
Uric acid is another biomarker that is totally misinterpreted dramatically. Again, people think about high uric acid for gout. Really, the big problem for longevity in neurology is low uric acid. When your uric acid levels get low, basically, it's an indicator of NAD deficiencies. Virtually, all neurological diseases. Parkinson's, Alzheimer's, MS, central nervous system viral infections, all of these will have low uric acid levels. Low uric acid is a good indicator of NAD deficiencies.
Low uric acid is a far more dangerous situation than high. Very interesting little tidbit. People with gout have higher cognitive functioning than people without gout. High uric acid is actually associated with high cognitive function. The ProdromeScan is designed as this Biochemistry 101 test. It looks at the key systems. It puts it all in one in your face, and you see, so you can interpret, you can understand the person in front of you. Was looking at, hey, is there a boogie man under the bed that had no way of knowing it's there?
Everything in there is modifiable through diet and supplementation and behavior. Then the goal is to get these core systems working. Then you can go into greater detail in other areas. There's thousands and thousands of types of tests that people can run.
[1:38:37] SCOTT: I think it's a very exciting test. I have a family member who just recently had the test done, which is part of what really spurred my interest into exploring your work in more detail. When would you suggest that someone do this testing, which looks at all of those factors, but also, is looking at the plasmalogens, if someone has no symptoms of cognitive decline, should it be done as a preventative screening, much like Dr. Bredesen talks about a cognoscopy? Then how often after doing the tests, should one repeat it to see if their supplemental exogenous plasmalogen precursors are moving them in the right direction?
[1:39:15] DR. GOODENOWE: Yeah. In general, you should get it as soon as possible. The other thing we do is we biobank your blood samples. When you get a blood sample sent to us, it doesn't get thrown in the garbage. It gets stored at minus 80 degrees. Three years later, we can go back and double check on things. That's the big thing. You want to get a computer restore point. The point is get the blood test, I would tell anyone to get it right away, and so you have the blood sample sitting in the freezer for future reference. But also, get an understanding, is there anything that might be doing other things, and I think is right, but is it actually doing what I want it to do, right?
Then from there, you can get a quick homework assignment of depending upon what you need to optimize. Then about three months later, you can do a follow up-test. Then after that, once a year is fine. Just keep an eye on things and do the things that you're excited about doing. The goal here is to reduce this unpredictable fear. People are worried. A lot of this health is a walk down the street. I get hit by lightning and I have a disease. Where the hell did it come from?
You live in this fear that of the unknown. The test is designed not to solve every single problem in the world, but look at the big ones and say, okay, there's not these really big lurking dangers. Then you can check on a semi-regular basis that you're on the right track. That's the concept of it. We'll expand it. There's some other core components that we'll add.
[1:40:45] SCOTT: In the plasmalogen precursor realm, you have the ProdromeNeuro, which is the Omega-3 plasmalogens, the ProdromeGlia, which is the Omega-9 plasmalogens. How long would someone normally take these exogenous plasmalogen precursors to really improve their symptoms to optimize their plasmalogens? Then once their levels are restored, is that something they generally need daily for life? Or is there then a maintenance period, or a pulsing strategy? What's the long-term picture look like?
[1:41:16] DR. GOODENOWE: People should think of it like vitamins, in a sense, right? You can go and get your B12 test done, for example. But does that mean you stop taking B12 supplements? No. You still want the nutritional optimization of our food supply. I think you do for the rest of your life, fundamentally. You treat it that way. It's a precursor. It's not, you measure the blood levels to show that you refilled the tanks, okay, which is great. I take plasmalogens every single day. I take my neuro in the morning, my glia at night. Trust me, my levels are good, because I make the stuff.
Every day I take it, because I feel it gives me that energy every morning. It's a precursor. Every day, it has a 12-hour – the tank gets filled, but you get this boost in your cells every day. That was the other real interesting thing over the last couple of years that we've seen so many people in my own personal experience, is that there is an acute benefit, as well as a long-term benefit. We don't know all the answers. We know from an epidemiological perspective, these low levels are bad. We don't know what the optimal levels really are.
These kids, these kids with rare diseases, local dystrophies, they're on really high doses. They're 10 mils or more. They're drinking this stuff and getting better. Again, that's what I'm telling you before, that scientists have to be really careful about the arrogance of science. Sometimes, we have to remember, we never, ever know everything. We work on the best approximations, and then make sure you have a feedback loop with yourself. You are always the best determiner of what's working. People should expect results from their programs.
[1:43:02] SCOTT: I'm guessing just with the level of cognition that you have that you're probably taking at least a full bottle of those every day. Something –
[1:43:10] DR. GOODENOWE: Not quite that much.
[1:43:11] SCOTT: Something is working. Just to clarify, I'm sure people have the question. My understanding is that the raw materials that go into these supplements are all vegan, vegetarian, that they're plant derived. They do not contain any fish oils, or any animal type products. Correct me if I'm wrong on that.
[1:43:27] DR. GOODENOWE: Yeah, absolutely. Yeah, the capsule, the gelatin capsules, of course, are not vegan. I think there's a new version coming up that have that, but they come in a full oil form. Yeah, it is very important. This is a highly pure manufacturing process. Okay, so we take the omega-3 plasmalogens, which is the DHA fatty acid. We drive that fatty acid from algae oil, a high purity, high DHA concentration. We take that algae oil, the stuff that you would normally buy on Amazon, or wherever you buy your supplement. We take that and we actually digest it. We saponify it. The way you make soap. We strip all the fatty acids off of the glycerol backbone, because that's just a regular triglycerol, just like your oil in your cupboard, for example.
We strip off the glycerol backbone, we get the pure fatty acid. Then we purify the DHA component of it. We go from a regular algae oil, we'll have maybe 50%, 60%, maybe if you're lucky, around that 50% to 60% omega-3 in it. We then take it through a purification process, and it becomes 95% omega-3. It's the highest purity concentrated omega-3 in the world, DHA. Then we take that purified DHA, which is from an animal, from a plant source, from the algae source. Then we put it on a plasmalogen backbone, and then we put it in the bottle. That's it. There's nothing in it. We have clove oil and cinnamon oil over time, because those high polyunsaturates have – they get oxidative stress over time. That will probably remove it.
That's how the omega-9, that's how the omega-3 ProdromeNeuro was made. That's why it's really high purity omega-3, and it's very – the bioavailability is really quite amazing. Then the omega-8, we get the oleic acid, we take that from a plant source, from a high oleic acid sunflower oil. Okay, again, same process. It's 95% oleic acid type oil. We saponify it to get the free fatty acid, purify it, and then we put it on. Now you get two very pure sources. You get a very high purity omega-9, that when you take it, it goes directly into these all good under sights of your cells. It goes right into the white matter with a very high potency. Then the omega-3, again, it's very high potency, very specific for very purpose. That's why it works. It's pretty cool. That's why it’s made.
[1:45:54] SCOTT: Are there any contraindications, or any common side effects that people have with plasmalogen precursor supplements?
[1:46:03] DR. GOODENOWE: No. Nothing directly. The oil, the DHA oil has a bit of a taste to it, if you take the liquid form, okay. I still take the liquid, because I like the faster acting. The gelatin capsules, but then I'm used to it. A lot of people say, they can't take the oil. It just tastes too bad. That's just life. The gel capsules are fine. The negative side effects, really, for people with ADHD, for example, and autism, I tell them to be cautious about the omega-3. It gets them, I got to peel them off the wall, because it's quite activating.
Glia is the calming nature for the ADHD people. People can adjust their dose for sleep at night. Some of our staff, they'll say, “If I take eight capsules, I have a hard time getting up in the morning, because I'm sleeping so deeply.” Then, so they take it down to four to six capsules at night.” It's a back and forth process. The negative side effects, really, there isn't anything that we have. We have these kids with rare diseases on massive doses. There'll be some people with a little bit GI, but normally it fixes GI issues. A lot of people, their GI, the Glia, especially, really improves gut function. Yeah, no. Contradictions, we haven't seen any.
[1:47:18] SCOTT: I'm going to have to get out my ProdromeGlia and my Oura Ring and see how my sleep shifts with that. That sounds like another fun little experiment to do.
[1:47:27] DR. GOODENOWE: We do find people – some people have to back it off from nighttime. I take mine right at bedtime. In simple things, it's weird, restless legs syndrome. If you take a high dose of the glia, it'll get rid of the restless legs and a lot of people, too.
[1:47:38] SCOTT: Wow.
[1:47:39] DR. GOODENOWE: But some people say, it actually wakes me up at night, because it actually reduces inflammation and go, oh, they're awake at night. They take it earlier, say, three or four hours. If you do find that glia is not putting to sleep right away, and it's actually making you awake a bit more than likely be, then just back a few hours before bedtime is what people tell me.
[1:48:00] SCOTT: My last question is the same for every guest, and I'm going to adapt it slightly for you. What are some of the key things that you do on a daily basis in support of your own health? Then what are some of the key supplements that you prioritize for your own health optimization?
[1:48:14] DR. GOODENOWE: Yeah. I'm a big believer. I’ll tell you exactly what I take every day. I'm a coffee drinker. In my morning coffee, I put a scoop of creatine in it and a scoop of collagen proteins. That's just, I just mix it with my coffee.
[1:48:29] SCOTT: That's why your skin looks so good, probably, right?
[1:48:33] DR. GOODENOWE: That's my coffee. I make all my B vitamins. I have a 100 milligrams of B1 thiamine, 100 milligrams of B2 riboflavin, take 500 milligrams of niacin. I take the not the niacinamide, not the not the anti-flush, but the actual flushing kind. I take a slow release capsule, 500 milligrams. I take some branch chain amino acids with that, because that branch chain amino acids improve niacin function. Then I take my carnitine. I take about a couple grams of carnitine a day. Twice a day, acetyl L carnitine, CoQ10. I take 100 milligrams of that. N-acetyl cysteine, I'm a big fan of that. I take 2 grams of that a day, a gram in the morning, a gram late afternoon.
These curcuminoids, which are these GTAs, BDMC, we have a special formulation that's really about 50 to a 100 times more potent than the regular turmeric. Has the special curcuminoid in it. I take three capsules of that a day, it says the curcuminoids. Then the methyltransferase system, I take a B12, take a milligram of that. Take a methyl folate, 100 milligrams of B6. Every now and then, every day or so, I'll take maybe an alpha-lipolic acid and a betaine on the methyltransferase system. I think that's about it every day. Just a multi mineral – that's basic stuff.
Then from a nutritional perspective, I'll make a little shake. We'll have nutrient shakes, but you can get egg yolk powder, powdered egg yolk. You can make smoothies with it. I make a little cocktail, like a whey protein, egg yolk powder, and I mix it with some coconut milk, the pure stuff, the cooking coconut stuff, right? Not the coconut drink stuff. The actual pure coconut stuff. That's a nice, little good fat, good protein, got your phospholipids in there. Then you can have a little half a cup, a little bit of that with my supplements, right? I can just have that. Oh, then I'll put a scoop of Trehalose in there. I'll sweeten it with Trehalose, and then I'll put a little bit of maple syrup for sweetening. Don't get any of that artificial sweetener stuff, but maple syrup itself has very low glycemic index. People think sugar, sugar always has these glycemic indexes. That's not true. The maple syrup has actually a very low insulin response.
Trehalose is a real amazing little sugar. What it basically is, it's a disaccharide. It's a two-glucose molecules, and it's a slow releasing glucose. Say, when you take a starchy high glycemic index carbohydrate, like a potato or something, that gets digested very quickly into glucose, so you get this glucose spike. This is what causes this glycemic index spike of insulin sensitivities that we have with meals.
Trehalose is a slow releasing sugar. It's sweet. It's a sweetener, but it's a slow releasing sugar. What it does, not only is it slow releasing, it actually blocks the fast release of glucose from regular carbohydrates. If you drink Trehalose before a meal, it will reduce the insulin spike of your meal. If I go to McDonald's and have a Big Mac and fries, then, but if I have a, say, a Trehalose drink 20, 30 minutes before that, the insulin effect of my Big Mac meal will be half.
[1:51:57] SCOTT: I'm guessing, you don't actually eat Big Mac meals.
[1:52:02] DR. GOODENOWE: I eat everything every now and then. No, I don't eat a lot of Big Macs. I'll have fatty ribs. I have guilty pleasures as well. That's where Trehalose, because so you add the sweetener, then I just add a little bit of, and you can get some good chocolate syrups that are just – that are made with the right pure sugars, right? If you get those right sugars, they're not bad for you. That’s where the Trehalose, basically, cuts the amount of other. That's what I have.
[1:52:29] SCOTT: I feel like your next book needs to be a recipe book for highly optimized people that we could start putting some of these things together. I'm a big fan of my power shake every day as well. I've had my tablespoon of PC blend this morning, also. I just loved the whole conversation. You were very generous with your time, but I learned a lot, connected lots of little dots. I mean, there were sentences you threw out here and there that connected more things for me. The book is amazing. They say that if you want to be smarter, to surround yourself with smarter people, and today spending time with you, I definitely feel a little bit smarter. Thank you so much, Dr. Goodenowe, for all the work that you do and for spending time with us today.
[1:53:11] DR. GOODENOWE: Thank you, Scott. It was a pleasure.
[END OF EPISODE]
[1:53:13] SCOTT: To learn more about today's guest visit DrGoodenowe.com. That's DrGoodenowe.com. DrGoodenowe.com.
[1:53:23] SCOTT: Thanks for listening to today's episode. If you're enjoying the show, please leave a positive rating, or review as doing so will help the show reach a broader audience. To follow me on Facebook, Instagram, Twitter, or TikTok, you can find me there as BetterHealthGuy. If you'd like to support the show, please visit BetterHealthGuy.com/donate. To be added to my newsletter, visit BetterHealthGuy.com/newsletters.
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